Myelofibrosis

INTRODUCTION

Myelofibrosis (MF) is a type of blood cancer that is closely connected to myeloproliferative neoplasms (MPNs), in which the bone marrow cells that make the body’s blood cells develop and behave improperly. Excessive fibrous (scar) tissue production in the bone marrow is the outcome, which can cause severe anemia, weakness, weariness, enlargement of the spleen and liver, and bodily wasting (loss of body mass or size). 

MF can develop on its own or because of the advancement of other MPNs, such as polycythemia vera (PV) and essential thrombocythemia (ET). PV or ET are the starting points for 15 to 20 percent of MF cases. Agnogenic myeloid metaplasia, chronic idiopathic myelofibrosis, and myelosclerosis with myeloid metaplasia are some of the various names for MF. 

What is Myelofibrosis? 

Myelofibrosis is a rare bone marrow cancer that causes fibrous (scar) tissue to replace the marrow. The soft, fatty tissue inside the bones is known as bone marrow. When a mutation in the DNA of a single hematopoietic (blood-forming) stem cell occurs, cancer develops. Bone marrow stem cells can divide and multiply into a variety of specialized cells that make up the bone marrow and blood. The mutations are passed on to new cells as the mutated bone marrow cell replicates and divides. This abnormal cell production eventually outnumbers the bone marrow’s ability to generate enough normal blood cells, such as red blood cells, which transport oxygen to tissues; white blood cells, which fight infection; platelets, which aid in blood clotting. 

How Does Myelofibrosis Develop? 

MF develops in bone marrow stem cells after a genetic mutation. A mutation in the Janus kinase 2 gene (JAK2) affects 50 to 60 percent of patients with MF, while a mutation in the calreticulin gene affects about 25 percent. Several additional mutations have lately been discovered in MF patients. Other probable gene variants linked to MF are being investigated by researchers. The reason for the gene mutation or the disease is unknown.  MF generally progresses slowly, and some people may go years without experiencing any symptoms. Other patients’ bone marrow may deteriorate over time and require treatment. Patients must be monitored on a frequent basis in both circumstances. 

Types of Myelofibrosis 

The type of MPN is determined by the excess of red blood cells, white blood cells, or platelets. The body can create too many types of blood cells at times, although white blood cells are usually affected more than the others. There are six forms of chronic myeloproliferative neoplasms: 

• Chronic myelogenous leukemia. 
• Polycythemia vera. 
• Primary myelofibrosis (also called chronic idiopathic myelofibrosis). 
• Essential thrombocythemia. 
• Chronic neutrophilic leukemia. 
• Chronic eosinophilic leukemia.  

Sources:  

https://www.mayoclinic.org 

SYMPTOMS AND SIGNS OF MYELOFIBROSIS

Myelofibrosis, also known as chronic idiopathic myelofibrosis, is a rare type of blood cancer that affects the bone marrow, the spongy tissue within bones that creates blood cells. Myelofibrosis leads to bone marrow fibrosis, where the bone marrow is scarred, and blood cell production will be affected. Myelofibrosis is an indolent cancer, so it develops slowly over several years. 

Myelofibrosis belongs to a larger group of blood cancers called myeloproliferative neoplasms (MPNs) where the bone marrow produces abnormal blood cells. Other MPNs include:  

• Chronic eosinophilic leukemia 
• Polycythemia vera 
• Chronic myelogenous leukemia 
• Essential thrombocythemia 
• Chronic neutrophilic leukemia 

When myelofibrosis develops on its own and not from other blood or bone marrow diseases, it is referred to as primary myelofibrosis (PMF). When another MPN such as polycythermia vera or essential thrombocythemia causes myelofibrosis to develop, it is referred to as secondary myelofibrosis (SMF). It is believed that only 10 to 20 percent of all myelofibrosis cases are SMF. 

There are two other classifications of myelofibrosis, prefibrotic myelofibrosis (pre-PMF), and autoimmune myelofibrosis. Pre-PMF is an early but aggressive form of myelofibrosis that eventually behaves like essential thrombocythemia and shares similar treatment options. Autoimmune myelofibrosis is a rare subset of PMF that behaves more like an autoimmune disease and is linked to systemic lupus erythematosus.  

Myelofibrosis Symptoms 

The symptoms of myelofibrosis can vary in each patient since the disease lasts for years and progresses slowly. In about one third of all cases, patients don’t experience any symptoms. However, in some patients the disease develops more quickly and will require treatment right away. All patients should get monitored regularly by their hematologist, whether symptoms are present or not.  

Common myelofibrosis symptoms include: 

• Night sweats 
• Persistent fatigue 
• Anemia 
• Higher blood pressure than normal 
• Swollen liver or spleen 
• Easily bruising or bleeding 
• Infections from lack of white blood cells (Neutropenia) 
• Itchy skin 
• Fever 
• Unexplained weight loss 
• Blood clots 
• Internal bleeding in the stomach or esophagus 

Symptoms are the biggest factor for doctors choosing which treatment option is most suitable for the patient. More intensive treatments are given to those with serious complications from the disease. Therefore, the above symptoms are signs that myelofibrosis is progressing. Although, in most cases of myelofibrosis, the goal of treatment is palliative, to relief symptoms and improve quality of life. Also, treatment helps reduce the size of enlarged spleens, improve counts of blood cells, and reduce the risk of other complications. 

Myelofibrosis Causes 

Like most other cancers, an error in one of your genes can cause the body to make cells that don’t function properly, leading to an overproduction of cells. In myelofibrosis this change occurs in the stem cells that make blood in the bone marrow. As these altered cells spread, your body will make less healthy blood cells. These cells eventually are inflamed, and scar tissue will form. In most myelofibrosis cases, the change is in one of three genes, JAK, CALR, or MPL. Researchers have been unable to identify the cause of these genetic changes, but research continues to learn more about this disease. The cause of these changes being inherited from family members has been ruled out. Researchers claim there is no way to prevent myelofibrosis from developing, but there are several known risk factors. For example, the average age at diagnosis is roughly 60 years old. In rare cases, long-term exposure to toxic chemicals like benzene or radiation can increase your risk of myelofibrosis developing. 

Sources: 

https://www.lls.org 

https://www.webmd.com 

MYELOFIBROSIS STATISTICS

Since myelofibrosis is a rare disease connected to myeloproliferative neoplasm, the statistical information relating to it is limited. About 20 percent of primary myelofibrosis patients do not manifest any symptoms and are diagnosed through a blood test intended for something else. The course of myelofibrosis is mostly indolent, but in some cases, it progresses more rapidly and transforms into a type of leukemia. This transformation is called acute myeloid leukemia (AML), which is seen among 10 to 20 percent of cases in a period of 10 years. 

The Survival Rate 

The median survival rate for myelofibrosis patients is between 3.5 and 5.5 years. When the patient is under the age of 55, and the prognostic factors are good, the median survival rate increases to 11 years. This being noted, there are many patients who continue their lives even with an MF diagnosis. Some risk factors listed under the International Prognostic Scoring System (IRSS) affect the median survival rates. The list goes as follows: 

• Being 56 years old or older 
• Having a level of hemoglobin under 10 grams per deciliter 
• Presenting symptoms such as night sweats, fever or weight loss 
• Having an elevated white cell count over 30,000/microL 
• Having at least 1 percent blood cells 

The patients who do not have the above-listed values, except for the age factor, have a median survival rate of more than 10 years. If the patient has two or more of these risk factors the median survival rate drops under 3 years.

Although there are some treatment options such as blood transfusions, drug therapy, radiation therapy and splenectomy, allogeneic hematopoietic stem cell transplant (allo-HSCT) is the only curative treatment option today. Recent studies show that JAK inhibitors help patients have positive outcomes of their therapies and a longer lifespan. Scientists all over the world are actively searching to find more about this rare disease. The number of active clinical trials worldwide focusing on myelofibrosis is over 120. 

Myelofibrosis Statistics Worldwide 

Primary myelofibrosis is considered to affect approximately 1 in 500,000 people worldwide. In the United States, the incidence is estimated to be 1.5 cases per 100,000 people. This rate drops to 0.5 cases per 100.000 people in the Northern European countries. 

Myelofibrosis Statistics by Age  

The rate of female and male primary myelofibrosis patients is equal. Although the patients diagnosed with this disease are typically over 50, it can affect people of any age. The average age of diagnosis is near 65. In children, the average age of diagnosis is about 3. MF is twice as common in girls compared to boys. 

Sources: 

rarediseases.org 

nature.com 

my.clevelandclinic.org 

leukaemia.org.au 

medicalnewstoday.com 

managedhealthcareexecutive.com 

MYELOFIBROSIS TREATMENT OPTIONS

Treatment for myelofibrosis (MF) is determined by your symptoms. If you aren’t in pain right now, you may be able to wait and watch without having to treat your cancer. Regular checks and blood tests can ensure that you don’t have any issues, such as anemia or spleen enlargement. 

Each patient is affected by MF in different ways. Your doctor can arrange your therapy based on your age, blood cell counts, amounts of immature blood cells called blasts, and symptoms including anemia or severe weight loss. 

Treatment for Anemia 

If myelofibrosis is causing severe anemia, you may consider treatments, such as: 

• Blood transfusions: If the patient has severe anemia, periodic blood transfusions can increase your red blood cell count and ease anemia symptoms, such as fatigue and weakness. Sometimes, medications can help improve anemia. 
• Androgen therapy: Taking a synthetic version of the male hormone androgen may promote red blood cell production and improve severe anemia in some patients. Androgen therapy does have risks, including liver damage and masculinizing effects in female patients. 
• Thalidomide and related medications: Thalidomide (Thalomid) and the related drug lenalidomide (Revlimid) may help improve blood cell counts and may also relieve an enlarged spleen. These drugs may be combined with steroid medications. Thalidomide and related drugs carry a risk of severe birth defects and require special precautions. 
• Interferon alfa-2a: Your doctor might try injections of these man-made versions of cells your body creates to fight tumors. It could cause depression or worsen problems like diabetes, immune disorders, and thyroid conditions. 

Treatment for an Enlarged Spleen 

If an enlarged spleen is causing complications, your doctor may recommend treatment. Your options may include: 

• Targeted drug therapy: Targeted drug treatments focus on specific abnormalities present within cancer cells. Targeted treatments for myelofibrosis focus on cells with the JAK2 gene mutation. These treatments are used to reduce symptoms of an enlarged spleen. 
• Chemotherapy: Chemotherapy uses powerful drugs to kill cancer cells. Chemotherapy drugs may reduce the size of an enlarged spleen and relieve related symptoms, such as pain. 
• Surgical removal of the spleen (splenectomy): If the spleen becomes so large that it causes pain and harmful complications — and if the patient does not respond to other forms of therapy — they may benefit from having the spleen surgically removed. 

• Risks include infection, excessive bleeding, and blood clot formation leading to stroke or pulmonary embolism. After the procedure, some patients experience liver enlargement and an abnormal increase in platelet count. 
• Radiation therapy: Radiation uses high-powered beams, such as X-rays and protons, to kill cancer cells. Radiation therapy can help reduce the size of the spleen when surgical removal isn’t an option. 

Treating Mutated Genes 

In a laboratory, doctors will analyze your blood or bone marrow cells for gene mutations, such as JAK2, CALR, and MPL. Your doctor uses the information from these tests to determine your prognosis and your treatment options. 

Bone Marrow Transplant  

A bone marrow transplant, also known as a stem cell transplant, is a surgery that uses healthy blood stem cells to replace the damaged bone marrow. The method for myelofibrosis uses stem cells from a donor (allogeneic stem cell transplant). 

Although this treatment has the potential to cure myelofibrosis, it comes with a high risk of life-threatening adverse effects, including the possibility that the new stem cells would react against the healthy tissues present in the patient’s body. 

Many patients with myelofibrosis do not qualify for this treatment because of age, stability of the disease, or other health problems. 

Prior to a bone marrow transplant, the patient receives chemotherapy or radiation therapy to destroy the diseased bone marrow. Then receives infusions of stem cells from a compatible donor. 

Myelofibrosis Clinical Trials 

Massive Bio specializes in finding advanced clinical treatments for every type of myeloproliferative neoplasms (MPNs). If you’ve been diagnosed with any of the following MPN subtypes, we’re here to help. If you don’t know which type of MPN, you have, that’s okay. You can request a free consultation from our experts. Additional testing can help you determine your exact diagnosis. 

• Primary Myelofibrosis (also known as chronic idiopathic myelofibrosis) 
• Chronic Myelogenous Leukemia 
• Essential Thrombocythemia (ET) 
• Chronic Neutrophilic Leukemia 
• Chronic Eosinophilic Leukemia 
• Polycythemia Vera Treatment (PV) 
• Multiple Myeloma Treatment 

Sources:  

https://www.mayoclinic.org 

LIVING AND MANAGING MYELOFIBROSIS

A diagnosis of myelofibrosis can be concerning, especially when many people have no symptoms at first. Myelofibrosis is a dangerous condition that scars bone marrow, stopping it from producing healthy blood cells. 

Many people with the illness now have a better prognosis thanks to advancements in treatment. However, it’s tough to predict how your life will alter once you’ve been diagnosed. The course of the disease and the prognosis differ greatly from one person to the next. 

Coping With Emotional and Social Effects 

Any chronic illness diagnosis can cause stress. It’s critical that you get the help of family, friends, or a support group. To deal with your feelings, you might wish to consider counseling. 

Try to maintain a manageable daily routine that includes: 

• Time for visits, activities, hobbies  
• Plan time to spend with friends and family   
• Take a walk or do some light gardening  
• Read a book or listen to music  
• Watch a movie that makes you laugh and lifts your spirits  
• Consider meditation, yoga, or other activities that help you relax  
• Consider spiritual outlets 

Coping With Physical Side Effects 

All myelofibrosis treatments come with the possibility of side effects. Before you begin treatment, you should talk to your doctor about it. 

Treatment side effects are determined by a variety of factors, including the dosage, your age, and whether you have any other medical conditions. The following are possible side effects: 

• Nausea: Your condition may cause organs other than your bone marrow (e.g. your spleen and liver) to produce red blood cells; if the spleen or liver start to produce red blood cells, they may become enlarged. This can put pressure on the stomach, leading to abdominal pain, discomfort or indigestion. 
• Fever: Your condition may cause the cells of your immune system to release cytokines that lead to an inflammatory response in your body. This inflammation may cause you to develop a fever. 
• Weight loss: Your condition may cause you to lose weight; this may be because you feel less hungry due to early satiety (feeling full after only a small amount of food) or abdominal pain, discomfort or indigestion caused by an enlarged spleen or liver. It is important to note that not all weight loss is bad. Maintaining a healthy body weight as a result of regular exercise and a balanced diet is important. However, sudden or unintentional weight loss could be caused by your condition and should be discussed with your doctor. 
• Bone pain: Your condition may cause stem cells within your bones to multiply. This may stretch and stimulate the periosteum (the covering of the bone), which may be painful. 
• Fatigue: Your condition causes your bone marrow (the soft tissue inside some of your bones) to produce fewer red blood cells, and can result in anaemia – a common contributing cause of fatigue. This means that your body can’t transport oxygen as well, making it harder for your muscles to work. 
• Itching: Your condition could cause the cells of your immune system to release cytokines that lead to an inflammatory response in your body. This inflammation may cause your skin to feel very itchy. 
• Night sweats: Your condition could cause the cells of your immune system to release cytokines that cause an inflammatory response in your body. This inflammation may cause you to sweat a lot during the night. 

Keep in mind that most adverse effects are only temporary and will go away once you’ve finished your therapy. To manage these side effects, you may need to take additional medications. 

Coping With the Costs of Cancer Care 

Cancer treatment can be expensive. It may be a source of stress and anxiety for people with cancer and their families. In addition to treatment costs, many people find they have extra, unplanned expenses related to their care. For some people, the high cost of medical care stops them from following or completing their cancer treatment plan. This can put their health at risk and may lead to higher costs in the future. Patients and their families are encouraged to talk about financial concerns with a member of their health care team.  

Caring for a Loved One with Cancer 

Listen: This is often a challenge when a loved one faces a life-threatening diagnosis. Try to listen without judging and without “cheerleading.” Your ability to sit with your loved one as they share those feelings is probably one of the most significant contributions you can make to your loved one’s well-being. 

Give advice only when you are asked: Friends and loved ones often take on the task of researching the diagnosis, treatment options or clinical trials. This can be very helpful, as the information is often overwhelming. What is not helpful is saying, “You ought to try this” or “You should do that.” Instead, let your loved one know you’ve done research and allow your loved one to decide if they want to know more. 

Educate yourself about cancer: CancerCare and other reputable organizations have helpful literature and user-friendly websites that provide detailed information about cancer treatments, side effects and other related concerns. 

Support your loved one’s treatment decisions: While you may be in a position to share decision-making, ultimately it is your loved one’s body and spirit that bear the impact of the cancer. 

Remember the caregiver: This is usually the spouse, partner, parent or adult child of the person with cancer. Caregivers take on necessary tasks such as driving to treatment, arranging medical appointments and providing needed care and emotional support. In many cases, they also take on many of the roles formerly handled by the person who has been diagnosed. The caregiver can also benefit from additional help with these tasks. 

Stay connected: Cancer treatment can be lengthy, and the cancer journey continues past the last day of treatment. People with cancer often note that friends and family “don’t call anymore” after the initial crisis of diagnosis. Checking in regularly over the long haul is both tremendously helpful and very meaningful for the person living with cancer. 

Keep things normal:  Often, we try to make life easier for the person going through cancer by “doing things” for them. It is a way of feeling useful at a time when we would otherwise feel helpless. However, it’s just as important to respect your loved one’s wishes to do normal “pre-cancer” tasks. For some people, being able to do things like cook dinner or continue working can lessen the sense that cancer is taking over their lives. Your loved one may not want to discuss their cancer and it might be helpful to make conversation that doesn’t involve their diagnosis. 

Be receptive to your loved one’s needs when treatment is over: This is often the time when people begin to process the enormity of what they have been through. Prior to this, they were deeply involved in, and distracted by, all the medical concerns such as getting treatment and coping with side effects. While your loved one may no longer need help getting through treatment, they may still need your emotional support. 

Be there: Think about how you’ve helped each other feel better during a difficult time in the past. This could be something as simple as sitting with your loved one during treatments. Do whatever works for you both, and don’t be afraid to try something new. 

Talking With Your Health Care Team About Side Effects 

Before starting treatment, talk with your doctor about possible side effects. Ask: 

• Which side effects are most likely? 
• When are they likely to happen? 
• What can we do to prevent or relieve them? 

Be sure to tell your health care team about any side effects that happen during treatment and afterward, too. Tell them even if you do not think the side effects are serious. This discussion should include physical, emotional, social, and financial effects of cancer. 

Sources: 

https://www.healthline.com 

https://www.leukaemia.org 

https://www.cancer.net 

MYELOFIBROSIS DIAGNOSIS

Doctors need specific tests to diagnose myelofibrosis. In some types of disease, the symptoms are not very pronounced. In addition, the disease can be seen differently in everyone. To determine the type and stage of myelofibrosis, doctors refer to a physical examination or various tests. 

Physical Examination 

As one of the most common symptoms of myelofibrosis is swelling in the spleen, your doctor will first perform a physical examination. The physical examination includes checks of the spleen, vital signs such as pulse and blood pressure, along with checks of lymph nodes and abdomen.  

During the physical exam, your doctor may ask you questions about: 

• Cardiovascular risk factors such as high blood pressure and diabetes 
• Past illnesses and injuries 
• Current and past medications and other treatments 
• History of thrombosis (formation or presence of a blood clot within a blood vessel) or hemorrhagic events (blood loss from damaged blood vessels) 
• Family medical history 
• Current symptoms 
• Weight loss 
• Tiredness 

Blood Tests  

People with primary myelofibrosis often have varying degrees of anemia. Anemia occurs when there are not enough healthy red blood cells to carry oxygen to your body’s organs. Blood tests check the number of blood cells, platelets, uric acid, bilirubin, and lactic dehydrogenase. 

• Complete blood count (CBC): Used to measure the number of red and white blood cells and platelets. In myelofibrosis, white blood cells and platelet counts may be higher or lower than expected. In addition, the amount of iron-rich protein (hemoglobin) that carries oxygen in red blood cells and the percentage of whole blood (hematocrit) made up of red blood cells are also measured by CBC. 
• Peripheral Blood Smear: The blood is examined under a microscope. The pathologist checks the appearance, shape, size, and presence of blast cells (immature blood cells) of the blood cells in the sample. Blast cells are not found in the peripheral blood of healthy individuals. People with MF often have abnormal teardrop-shaped red blood cells and immature blasts in the blood. 
• Blood Chemistry Profile: This blood test measures the levels of electrolytes (such as sodium, potassium, and chloride), fats, proteins, glucose (blood sugar), uric acid, and enzymes released into the blood by organs and tissues in the body; It gives information about how well a person’s kidneys, liver, and other organs are working. People with MF often have elevated serum uric acid, lactic dehydrogenase (LDH), alkaline phosphatase, and bilirubin levels. 

Bone Marrow Biopsy 

Doctors examine samples from the bone marrow with a microscope. They investigate the number and types of cells in the bone marrow and whether there is a mutation in JAK2. 

Gene Tests

Doctors look for abnormal changes in genes, chromosomes, proteins, or other molecules in a patient’s cancer cells. 

• Cytogenetic Analysis (Karyotyping): Investigates abnormal changes in the chromosomes of cancer cells. Healthy human cells contain 23 pairs of chromosomes for 46 chromosomes. Each chromosome pair has a specific size, shape, and structure. In some cases of MF, cancer cells have abnormal changes in their chromosomes that can be seen under the microscope, such as extra or missing chromosomes or broken or rearranged chromosomes. Some patients with MF have a “complex karyotype” that occurs when there are three or more unrelated abnormalities in the chromosomes. 
• Polymerase Chain Reaction (PCR): A susceptible test used to detect specific genetic mutations too small to be seen with a microscope. PCR testing essentially amplifies (amplifies) small amounts of specific DNA fragments so that they are easier to detect and quantify in a cell sample. It looks for the presence or absence of specific gene mutations. PCR testing can be done with blood or bone marrow samples. 
• DNA Sequencing: Examines the complete sequence of DNA. By comparing the DNA sequence in cancer cells with the DNA in normal cells, doctors can find genetic changes specific to cancer cells and drive the growth of a patient’s cancer. It can be done with blood or bone marrow samples.

Imaging Tests 

Ultrasound, magnetic resonance imaging (MRI), or X-ray tests may be done to check the enlargement of the spleen. Imaging Tests can look for changes in the bone marrow that could be signs of myelofibrosis and show changes in bone density that could be a sign of the disease. 

Sources: 

Lls.org 

Webmd.com 

Leukaemia.org.au 

Clevelandclinic.org 

MYELOFIBROSIS MUTATIONS

Myelofibrosis is a rare type of blood cancer that affects the bone marrow, the spongy tissue within bones that creates blood cells. Myelofibrosis leads to bone marrow fibrosis, where the bone marrow is scarred, and blood cell production will be affected. Myelofibrosis is an indolent cancer, so it develops slowly over several years. To test for mutations in myelofibrosis, a gene mutation test will be performed by a doctor. A laboratory test will analyze a bone marrow or blood sample for alterations in the commonly mutated genes in myelofibrosis, JAK2, MPL, TET2 and CALR genes. 

Myelofibrosis belongs to a larger group of blood cancers called myeloproliferative neoplasms (MPNs) where the bone marrow produces abnormal blood cells. Other MPNs include:  

• Chronic eosinophilic leukemia 
• Polycythemia vera 
• Chronic myelogenous leukemia 
• Essential thrombocythemia 
• Chronic neutrophilic leukemia 

When myelofibrosis develops on its own and not from other blood or bone marrow diseases, it is referred to as primary myelofibrosis (PMF). When another MPN such as polycythemia vera or essential thrombocythemia causes myelofibrosis to develop, it is referred to as secondary myelofibrosis (SMF). It is believed that only 10 to 20 percent of all myelofibrosis cases are SMF. 

Genetic Mutations and Myelofibrosis Treatments 

There are treatments that are either FDA approved or available in clinical trials to treat myelofibrosis with a mutation. Targeted therapies are drugs or other substances that identify and attack cancer cells with specific alterations. These therapies don’t target healthy cells, often causing less harm than chemotherapy or radiation. 

In myelofibrosis, Tyrosine kinase inhibitors (TKI) are a type of targeted therapy that blocks signals that cancer cells need to grow. Ruxolitinib is the first TKI that is FDA approved for myelofibrosis. 

Other standard treatments for myelofibrosis include: 

• Targeted therapy with ruxolitinib 
• Chemotherapy. 
• Donor stem cell transplant 
• Splenectomy 
• Thalidomide, lenalidomide, or pomalidomide 
• Radiation therapy to the spleen, lymph nodes, or other areas outside the bone marrow where abnormal blood cells are forming 
• Erythropoietic growth factors 
• Immunotherapies 
• A clinical trial for targeted therapy drugs 

JAK2 

In normal cells, The JAK2 gene provides instructions for making a protein that promotes the growth and division (proliferation) of cells. The JAK2 protein is part of a signaling pathway called the JAK/STAT pathway, which transmits chemical signals from outside the cell to the cell’s nucleus. The JAK2 protein is responsible for maintaining the production of blood cells from hematopoietic stem cells, which are in the bone marrow. These cells can develop into white blood cells, red blood cells, and platelets.  

The V617F mutation is found in roughly half of all myelofibrosis cases. In more rare cases, there are mutations in the exon 12 region of the gene. The mutation causes the JAK2 protein to be continuously activated, leading to an overproduction of abnormal megakaryocytes. Other cells are then stimulated by the megakaryocytes and release collagen, which normally provides structural support to other bone marrow cells. The released collagen leads to scar tissue forming in the bone marrow, also known as fibrosis. When fibrosis occurs, normal blood cells cannot be produced enough, causing the common signs and symptoms associated with myelofibrosis. 

CALR 

In normal cells, the CALR gene provides instructions for making calreticulin, a protein found in the endoplasmic reticulum (ER), the cytoplasm, and the outer surface of the cell. The ER is involved in protein transport and processing while calreticulin ensures newly formed proteins are folded properly. Also, the ER is a storage location for charged calcium atoms (calcium ions) and calreticulin helps maintain the correct levels of calcium ions. Calreticulin uses calcium regulation and other mechanisms to help control gene activity, movement, cell growth, cell division, connecting cells to one another (adhesion), and the regulation of programmed cell deaths (apoptosis). This protein’s function is important for the function of the immune system and healing wounds. According to researchers, it is unknown how mutations in exon 9 of CALR affect calreticulin function or how the altered protein is involved in myelofibrosis. 

TET2 

In normal functioning cells, the TET2 gene provides instructions for making a protein involved in the transcription of a cell, which is the first step in protein production. The TET2 protein is found throughout the body but is especially important in the production of blood cells from hematopoietic stem cells, which are located in the bone marrow. Healthy TET2 proteins are considered tumor suppressors, meaning they prevent cells from growing and dividing in an uncontrollable way. When a mutation occurs, this can lead to the spread and growth of abnormal cells in the bone marrow. It is still unclear to researchers how mutations in the TET2 gene affect the development of myelofibrosis. 

MPL 

In normal cells, the MPL gene provides instructions for making the thrombopoietin receptor protein, which promotes the growth and division (proliferation) of cells. This receptor is important in the proliferation of megakaryocytes, which are blood cells that produce platelets, the cells involved in blood clotting.  

The thrombopoietin receptor is activated by thrombopoietin, a protein that binds to the receptor. The JAK/STAT signaling pathway is stimulated by the activated receptor and transmits chemical signals from outside the cell to the cell’s nucleus and helps control blood cell production. Several mutations in the MPL gene have been identified in some myelofibrosis patients. These mutations lead to an activated thrombopoietin receptor protein that overproduces abnormal megakaryocytes. This causes other cells to release collagen that causes scar tissue formation. 

Sources: 

https://medlineplus.gov/mpl 

https://medlineplus.gov/calr 

https://medlineplus.gov/jak2 

https://medlineplus.gov/tet2

https://www.cancer.gov 

MYELOFIBROSIS RISK FACTORS AND PREVENTION

Myelofibrosis is a rare type of blood cancer that affects the bone marrow, the spongy tissue within bones that creates blood cells. Myelofibrosis leads to bone marrow fibrosis, where the bone marrow is scarred, and blood cell production will be affected. Myelofibrosis is an indolent cancer, so it develops slowly over several years.  

Myelofibrosis belongs to a larger group of blood cancers called myeloproliferative neoplasms (MPNs) where the bone marrow produces abnormal blood cells. Other MPNs include:  

• Chronic eosinophilic leukemia 
• Polycythemia vera 
• Chronic myelogenous leukemia 
• Essential thrombocythemia 
• Chronic neutrophilic leukemia 

When myelofibrosis develops on its own and not from other blood or bone marrow diseases, it is referred to as primary myelofibrosis (PMF). When another MPN such as polycythemia vera or essential thrombocythemia causes myelofibrosis to develop, it is referred to as secondary myelofibrosis (SMF). It is believed that only 10 to 20 percent of all myelofibrosis cases are SMF. 

While the exact cause of myelofibrosis is still being researched, there are several known risk factors and tips for preventing myelofibrosis. 

What Are the Risk Factors of Myelofibrosis? 

Although rare and most people have a low risk of myelofibrosis, there are several known risk factors. According to researchers, myelofibrosis risk groups include those with one or more of the following: 

• Age over 50: Myelofibrosis is diagnosed most often in those over the age of 50. 
• Another blood disorder: Other MPNs such as thrombocythemia or polycythemia vera can develop into SMF. 
• Exposure to petrochemicals: Exposure to industrial chemicals such as toluene and benzene are associated with developing myelofibrosis. 
• Exposure to radiation: Radioactive material exposure is associated with an increased risk of developing myelofibrosis. 

If you have predisposing factors of myelofibrosis present or had abnormal results in a complete blood count (CBC) test, a doctor will perform tests to confirm the myelofibrosis diagnosis such as: 

• Magnetic resonance imaging (MRI): View any changes in the bone marrow such as fibrosis 
• X-ray: Shows any changes in bone density, a sign of myelofibrosis 
• Ultrasound: Can determine if the spleen is enlarged 

These myelofibrosis screening methods can help determine if these underlying issues are from myelofibrosis or another cause. If the patient is diagnosed with myelofibrosis, these tests will help understand the extent of the disease. 

Genetic tests may also help determine one’s risk of developing myelofibrosis. Although there is a low myelofibrosis genetic risk, there are gene mutations that occur after birth that lead to the development of myelofibrosis. A majority of mutations are specific to the JAK2, MPL, TET2, and CALR genes. 

The underlying cause of PMF is still not understood entirely. Myelofibrosis is not inherited, but it does come from DNA changes in certain genes acquired over time. Proteins called janus-associated kinases (JAKs) play a role in many cases of myelofibrosis. JAKs regulate the production of blood cells in bone marrow by signaling the cells when to divide and grow. If the JAK proteins become overactive, too many or too few blood cells are produced. 

About half of all patients have a mutation in the JAK2 gene. Another 5 to 10 percent of patients have a mutation in the myeloproliferative leukemia (MPL) gene. A third of all myelofibrosis cases are associated with a mutation called calreticulin (CALR). When mutated cells grow and divide, the mutation is passed on to the new cells. Once there are more mutated cells than healthy blood cells, too many white blood cells or not enough red blood cells will be produced. The bone marrow is scarred (fibrosis) and hardens, as opposed to being soft and spongy normally. 

How Can Myelofibrosis Be Prevented? 

There is no way to guarantee myelofibrosis prevention today. Researchers are still learning about the underlying cause and ways to prevent MPNs such as myelofibrosis. If you are at risk, talk with your doctor about changes to your diet, lifestyle factors, and family history of MPNs, that may influence your prevention of myelofibrosis.  

The myelofibrosis prognosis is favorable for most patients and symptoms can be managed with palliative care. The only way to potentially cure myelofibrosis is an allogenic hematopoietic stem cell transplantation (HCT). A healthy donor provides some blood cells, often a sibling or other family member. Healthy blood cells are injected into the patient and will eventually target and kill the cancerous cells in the bone marrow. Most patients are given chemotherapy and/or radiation therapy prior to the procedure. 

However, there are complications with this procedure and not all patients are suitable for this treatment. Other new and alternative myelofibrosis treatments such as targeted therapies and immunotherapies are available to cancer patients of all stages and subtypes in clinical trials. 

Sources: 

https://my.clevelandclinic.org 

https://www.healthline.com 

MYELOFIBROSIS GLOSSARY

A 

• Acute myeloid leukemia (AML): Blood and bone marrow cancer. Conversion to acute myeloid leukemia occurs in 10 to 20 percent of myelofibrosis cases. 
• Acquired Von Willebrand’s Syndrome: The platelets interfere with the body’s normal clotting mechanism, can’t work, and there is abnormal bleeding. 
• Agnogenic myeloid metaplasia: A progressive, chronic disease in which the bone marrow is replaced by fibrous tissue and blood is made in organs such as the liver and the spleen, instead of in the bone marrow. 
• Allele: An allele is one of two or more versions of a gene. An individual inherits two alleles for each gene, one from each parent. If two alleles are the same, it is called homozygous, and if the alleles are different, it is called heterozygous. Allele refers to variation between non-coding DNA sequences. 
• Allogenic Stem Cell Transplant: A procedure in which a person receives blood-forming stem cells (cells from which all blood cells develop) from a genetically similar, but not identical, donor. This is often a sister or brother, but also could be an unrelated donor. 
• Anemia: A deficiency of red blood cells often accompanied by fatigue, weakness, and shortness of breath. 
• Apoptosis: The process of programmed cell death (PCD) that may occur in multicellular organisms. 
• Aurora Kinase Inhibitors: Substance which blocks enzymes (Aurora kinases) involved in cell division and may kill cancer cells. 
• Autologous Stem Cell Transplant: A transplant in which a patient’s own blood-forming stem cells are collected. He or she is then treated with high doses of chemotherapy, or a combination of chemotherapy and radiation. The high-dose treatment kills cancer cells, but also eliminates the blood-producing cells that are left in the bone marrow. 

B 

• Biotherapy: One of the methods used in the treatment of myelofibrosis. It is a type of treatment that uses the body’s immune system to prevent or slow tumor growth and prevent the spread of cancer. 
• Blood tests: Blood cells are investigated in relation to the suspected disease. High levels of uric acid, bilirubin, and lactic dehydrogenase may indicate the presence of myelofibrosis. 
• Bone marrow: Soft, spongy tissue that has many blood vessels and is located in the center of most bones. There are two types, red and yellow. Red bone marrow contains blood stem cells that can develop into red blood cells, white blood cells, or platelets. Yellow bone marrow is mostly made of fat and contains stem cells that can turn into cartilage, fat or bone cells. 
• Bone marrow biopsy: It is the process of taking a sample of bone marrow to examine under the microscope. 

C 

• CALR: It is a protein-coding gene. Most frequent somatic mutation after JAK2 in ET and PMF patients. The CALR gene provides instructions for making a multifunctional protein called calreticulin. This protein is found in various parts of the cell, including inside a structure called the endoplasmic reticulum (ER), the fluid-filled space inside the cell (cytoplasm), and the outer surface of the cell. The function of protein is important for immune system function and wound healing. Diseases associated with CALR include Myelofibrosis and Thrombocythemia. 
• CAR T – cell therapy: The process of harvesting cells from blood or bone marrow, which aregenetically modified before being expanded in number. This modification targets the T cells specifically to the patient’s cancer and triggers them to attack when they get there. 
• Chemokines: Any of various cytokines produced in acute and chronic inflammation that mobilize and activate white blood cells. 
• Chimeric Antigen Receptor (CART) cells: Cells taken from the body and programed to identify and kill cancer cells. 
• Chemotherapy: It is one of the powerful drugs used to kill cancer cells. Chemotherapy drugs can reduce the size of an enlarged spleen and relieve related symptoms such as pain. 
• Complete blood count (CBC): In the diagnosis of myelofibrosis, blood cells are checked by looking at the complete blood count. A high number of white blood cells and platelets and a lower-than-normal number of red blood cells can be signs of myelofibrosis. A complete blood count test measures several components and features of your blood, including: Red blood cells, which carry. 
• Cytokine: A type of protein that has an effect on the immune system. Some cytokines stimulate the immune system and others slow it down. Cytokines are often produced by immune cells but can also be produced by nonimmune cells. They can also be made in the lab and used therapuetically. 
• Cytopenias: A deficiency of some cellular element of the blood. 
• Cytoplasm: The protoplasm (the cytoplasm and nucleus of a cell) outside the nucleus of a cell. 

D 

• DNA sequencing: The term DNA sequencing refers to sequencing methods for determining the order of the nucleotide bases—adenine, guanine, cytosine, and thymine—in a molecule of DNA. 

E 

• Endothelial: A thin layer of flat epithelial cells that lines serous cavities, lymph vessels, and blood vessels. 
• Enlarged spleen: A common symptom for myeloproliferative Neoplasm (MPN) patients, which takes place once blood production begins taking place in the spleen. Infections, liver disease, and some types of cancer can cause the spleen to enlarge. An enlarged spleen is also known as splenomegaly. Patients will sometimes undergo a splenectomy to remove the spleen, and reduction in spleen is an outcome of several MPN drugs. 
• Erythropoietin: A hormone that stimulates production of red blood cells and hemoglobin in the bone marrow. 
• Essential thrombocythemia (ET): is an uncommon disorder in which your body produces too many platelets. Platelets are the part of your blood that sticks together to form clots. This condition may cause you to feel fatigued and lightheaded and to experience headaches and vision changes. 
• Extramedullary hematopoiesis: Abnormal growth of blood-forming cells outside the bone marrow. These cells may enter other parts of the body, such as the lungs, gastrointestinal tract, spinal cord, brain or lymph nodes. The cells can form masses (tumors) that compress organs or impair their function. MPN patients suffer from an enlarged spleen due to this. 

F 

• Fibrocytes: A cell that produces fibrous tissue; also called fibroblast. 
• Fibrosis: Thickening and scarring of connective tissue. Bone Marros fibrosis is investigated in the diagnosis of myelofibrosis. 
• FDA: The U.S. Food and Drug Administration.

G 

• Gene mutation analysis: Blood cells may be examined for certain mutations associated with myelofibrosis. 

H 

• Hematopoiesis: Is the process by which the body produces blood cells and blood plasma. It occurs in the bone marrow, spleen, liver, and other organs. 
• Hematopoietic cell transplantation (HCT): It is the transplantation of multipotent hematopoietic stem cells, usually from bone marrow, peripheral blood, or umbilical cord blood, to proliferate inside a patient and produce additional normal blood cells. There are 3 types of hematopoietic stem cell transplants: autologous (the patient’s own stem cells are used), allogeneic (stem cells come from a donor), or syngeneic (come from an identical twin). 
• Hemoglobin: The part of the red blood cell that carries oxygen. 

I 

• Idiopathic: Relating to or being a disease having no known cause. 
• Idiopathic myelofibrosis: Primary myelofibrosis is also called chronic idiopathic myelofibrosis. 
• Imaging tests: A type of test that makes detailed pictures of areas inside the body. Imaging tests use different forms of energy, such as x-rays (high-energy radiation), ultrasound (high-energy sound waves), radio waves, and radioactive materials. In myelofibrosis, an ultrasound test can be done to check the enlargement of the spleen. 
• Immunotherapy: Many cancer treatments can be thought of as immunotherapy. These treatents stimulate the patient’s immune system to fight the disease. Some treatments that are thought of as immunotherapy use immune system component (such as proteins called antibodies.) that are made in the lab. Some boost the immune system. Others target certain proteins that help cancer cells grow. This is called targeted therapy. 
• Immunomodulatory: Change in the body’s immune system, caused by agents that activate or suppress its function. 
• Inflammation: Is a process by which your body’s white blood cells and the things they make protect you from infection from outside invaders, such as bacteria and viruses. 
• Inhibitor: An agent that slows or interferes with a chemical action. A substance that reduces or suppresses the activity of another substance (such as an enzyme). 

J 

• Janus kinase (JAK): Is a family of intracellular, non-receptor tyrosine kinases (a type of enzyme that phosphorylates protein) that transmit signals via JAK-STAT. 
• JAK2: Jack 2 is a member of JAK family. It provides instructions for making a protein that promotes cells’ growth and division (reproduction). This protein controls how many blood cells the stem cells produce. 
• JAK2V617F: The genetic mutation found in approximately 50 % of myelofibrosis patients, 95 % of polycythemia vera patients, and approximately 50 % of essential thrombocythemia patients. 
• JAK2 V617F mutation test: A positive JAK2 V617F mutation test, along with other supporting clinical signs, means it is likely that the person tested has an MPN. Other testing, such as a bone marrow biopsy, may need to be performed to determine which MPN the person has and to evaluate its severity. 
• JAK/STAT: The pathway that transmits chemical signals from the outside of the cell to the cell nucleus. 
• Jakafi: The medicine used to treat certain bone marrow disorders (myelofibrosis, polycythemia vera). It works by preventing your body from producing substances called growth factors. 

L 

• Leukemia: Is cancer of the body’s blood-forming tissues, including the bone marrow and the lymphatic system. Many types of leukemia exist. Some forms of leukemia are more common in children. Other forms of leukemia occur mostly in adults. Leukemia usually involves the white blood cells.  
• Leukemiogensis: Induction, development, and progression of a leukemic disease. 
• Lymph nodes: A small bean-shaped structure that is part of the body’s immune system. Lymph nodes filter substances that travel through the lymphatic fluid, and they contain lymphocytes (white blood cells) that help the body fight infection and disease. There are hundreds of lymph nodes found throughout the body.

M 

• Macrophage: A large white blood cell, occurring principally in connective tissue and in the bloodstream that ingests foreign particles and infectious microorganisms by phagocytosis. 
• Megakaryocyte: A bone marrow cell responsible for the production of blood thrombocytes (platelets), which are necessary for normal blood clotting. Megakaryocytes normally account for 1 out of 10,000 bone marrow cells but can increase in number nearly 10-fold in certain diseases. 
• Memory loss: Myelofibrosis can cause memory loss, especially for people who are female, 60+ old. 
• Momelotinib: Is a potent, selective and orally-bioavailable JAK1, JAK2 inhibitor with a differentiated therapeutic profile in myelofibrosis (MF). Data from more than 820 patients with MF suggest that momelotinib can markedly improve constitutional symptoms and splenomegaly while also substantially addressing the chronic anemia and transfusion dependency associated with the disease. 
• Monoclonal antibodies: These are man-made versions of immune system proteins. Antibodies can be extremely useful in treating cancer because they can be designed to attack a very specific part of a cancer cell. 
• Monocyte: A type of white blood cell and is part of the human body’s immune system. Monocytes play multiple roles in immune function. 
• Morphogenesis: The constellation of biological processes that determine an organism’s shape, which is inextricably intertwined with cell growth and differentiation, the other key elements of developmental biology. 
• MPL: A gene that makes a protein that helps control the number of blood cells that are made in the bone marrow, especially platelets. Mutated (changed) forms of the MPL gene may cause the body to make abnormal blood cells or too many platelets. Is present in patients with MF and ET at a frequency of approximately 5 percent and 1percent, respectively. 
• Mutations: A mutation is a change in a DNA sequence. Mutations can result from DNA copying mistakes made during cell division, exposure to ionizing radiation, exposure to chemicals called mutagens, or infection by viruses. 
• Myelo: Is a combining form used like a prefix meaning “marrow” or “of the spinal cord.” It is often used in medical terms. Marrow is a soft, fatty, vascular tissue in the interior cavities of bones that is a major site of blood cell production. The bone marrow produces immature blood cells that can develop into specialized blood cells such as red blood cells, white blood cells, or platelets and give them to the blood. So that all the blood cells necessary for the body are produced healthily. 
• Myelofibrosis: An anemic condition in which bone marrow becomes fibrotic and the liver and spleen usually exhibit the development of blood-cell precursors. Is an uncommon type of bone marrow cancer that disrupts your body’s normal production of blood cells. Myelofibrosis causes extensive scarring in your bone marrow, leading to severe anemia that can cause weakness and fatigue. 
• Myeloid metaplasia: A progressive, chronic disease in which the bone marrow is replaced by fibrous tissue and blood is made in organs such as the liver and the spleen, instead of in the bone marrow. This disease is marked by an enlarged spleen and progressive anemia. Also called chronic idiopathic myelofibrosis, idiopathic myelofibrosis, myelosclerosis with myeloid metaplasia, and primary myelofibrosis. 
• Myeloproliferative disorder: Also known as myeloproliferative neoplasms (MPN). Are a unique group of hematopoietic stem cell disorders that share in common mutations which continuously activate JAK2, an enzyme that normally stimulates the production of red blood cells, white blood cells, and platelets. 
• Myelodysplastic syndromes (MDS): Are a type of rare blood cancer where you don’t have enough healthy blood cells. It is also known as myelodysplasia. There are many different types of MDS. Some types can stay mild for years and others are more serious. 

N 

• Neutropenia: A significant decrease in the number of white blood cells. 
• Non-receptor tyrosine kinases (NRTK): Are a sub-group of tyrosine kinases, which can relay intracellular signals originating from extracellular receptor. NRTKs can regulate a huge array of cellular functions such as cell survival, division/propagation and adhesion, gene expression, immune response, etc.  
• Non-specific immunotherapies: These treatments boost the immune system in a general way, but this can still help the immune system attack cancer cells. 

O 

• Oncogenic: An oncogenic process is any tumor-forming process. Oncovirinae, retroviruses which contain an oncogene, are categorized as such because they trigger the growth of tumorous tissues in the host. Oncogenesis is the process of malignant tumor growth. 
• Osteoblastic: A cell from which bone develops; a bone-forming cell. 
• Osteosclerosis: An elevation in bone density that can occur in people with an MPN. It is normally detected on an X-ray as an area of whiteness and is where the bone density has significantly increased. 

P 

• PD1 Inhibitors: PD1 means Programmed Cell Death. PD1s prevent the activation of T-cells, which reduce the body’s ability to protect itself with its immune system. A new class of cancer drugs that block PD-1, the PD-1 inhibitors, activate the immune system to attack tumors to varying degrees of success. 
• Petechiae: Flat, red, pinpoint spots under the skin caused by bleeding. 
• Phagocytosis: The process by which a cell, such as a white blood cell, ingests microorganisms, other cells, and foreign particles. 
• Phlebotomy: The act or practice of opening a vein by incision or puncture to remove blood as a therapeutic treatment. Also called venesection. 
• Phenotype: Any observable characteristic or trait of an organism: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior. 
• Platelets (thrombocytes): Are colorless blood cells that help blood clot. Platelets stop bleeding by clumping and forming plugs in blood vessel injuries. Thrombocytopenia might occur as a result of a bone marrow disorder such as leukemia or an immune system problem. 
• Pluripotency: Pluripotent means many. A pluripotent cell can create all cell types except for extra embryonic tissue, unlike a totipotent cell, meaning all, which can produce every cell type including extra embryonic tissue. 
• Portal hypertension: Portal hypertension is elevated pressure in your portal venous system. The portal vein is a major vein that leads to the liver. The most common cause of portal hypertension is cirrhosis (scarring) of the liver. 
• Polycythemia: Polycythemia, also known as erythrocytosis, means having a high concentration of red blood cells in your blood. This makes the blood thicker and less able to travel through blood vessels and organs. 
• Polycythemia vera (PV): Is a rare blood disorder in which there is an increase in all blood cells, particularly red blood cells. The increase in blood cells makes your blood thicker. This can lead to strokes or tissue and organ damage. 
• Primary myelofibrosis: A progressive, chronic disease in which bone marrow is replaced by fibrous tissue and blood is made in organs such as the liver and spleen instead of the bone marrow. It is characterized by the accumulation of scar tissue (fibrosis) in the bone marrow, the tissue that produces blood cells. Due to fibrosis, the bone marrow cannot produce enough normal blood cells. 
• Pruritis: Severe itching. A common symptom of people with MPNs. 

R 

• Radiotherapy: Radiation therapy (also called radiotherapy) is a cancer treatment that uses high doses of radiation to kill cancer cells and shrink tumors. 
• Red blood cells: A type of blood cell that is made in the bone marrow and found in the blood. Red blood cells contain a protein called hemoglobin, which carries oxygen from the lungs to all parts of the body. Checking the number of red blood cells in the blood is usually part of a complete blood cell (CBC) test. It may be used to look for conditions such as anemia, dehydration, malnutrition, and leukemia. Also called erythrocyte and RBC. 
• Ruxolitinib: Ruxolitinib is a medication used to manage and treat myelofibrosis, polycythemia vera, and steroid-refractory acute graft-versus-host disease. It is in the Janus Kinase inhibitor class of medications. 

S 

• Secondary myelofibrosis: Secondary myelofibrosis refers to the bone marrow fibrosis that sometimes forms in people who were first diagnosed with polycythemia vera or essential thrombocythemia. Secondary myelofibrosis is sometimes referred to as a fibrotic phase of essential thrombocythemia or polycythemia vera. 
• Splenectomy: A splenectomy is the surgical procedure that partially or completely removes the spleen. If your spleen becomes so large that it causes you pain and begins to cause harmful complications — and if you don’t respond to other forms of therapy — you may benefit from having your spleen surgically removed. 
• Splenomegaly: See; enlarged spleen. 
• Stem cell transplantation: A procedure in which a patient receives healthy stem cells (blood-forming cells) to replace their own stem cells that have been destroyed by treatment with radiation or high doses of chemotherapy. 
• Stroke: Rapid loss of brain function due to a disturbance of blood flow to the brain such as a blockage or hemorrhage. 

T 

• Thrombocythemia: Thrombocytosis is a disorder in which your body produces too many platelets. It’s called reactive thrombocytosis or secondary thrombocytosis when the cause is an underlying condition, such as an infection. 
• Thrombocytopenia: An abnormal decrease in the number of platelets in circulatory blood. 
• Thrombocytosis: The body produces a surplus of platelets (thrombocytes). 
• Thrombopoietin (TPO): A hormone produced mainly by the liver and the kidney that regulates the production of platelets by the bone marrow. It stimulates the production and differentiation of megakaryocytes, the bone marrow cells that fragment into large numbers of platelets. 

U 

• Uric acid: Is a chemical created when the body breaks down substances called purines. Most uric acid dissolves in blood and travels to the kidneys. From there, it passes out in the urine. If the body produces too much uric acid or does not remove enough of it, you can get sick. A high level of uric acid in the blood is called hyperuricemia. If a person has myelofibrosis, the patient’s body produces more uric acid than usual. 

V 

• Vonjo: is a prescription medicine used to treat the symptoms of Myelofibrosis. Vonjo may be used alone or with other medications. Belongs to a class of drugs called Antineoplastics, Tyrosine Kinase Inhibitor; Antineoplastics, JAK Inhibitors. 

W 

• White blood cells: White blood cells are part of the body’s immune system. They help the body fight infection and other diseases. 

Sources: 

Cancer.cov 

Cancercentrelondon.co.uk 

Genome.gov 

Haematologica.org 

Hopkinsmedicine.org 

Lls.org 

Mayoclinic.org 

Medlineplus.gov 

Merriam-webster.com 

Ncbi.nlm.nih.gov 

Rxlist.com  

Sierraoncology.com 

Webmd.com 

MYELOFIBROSIS CLINICAL TRIALS

The aim of clinical trials, in general, is to improve the effectiveness of an existing drug or treatment, develop new procedures, improve the patients’ quality of life, or create an innovative treatment. Any kind of treatment, drug, or procedure that is available for patients now was once studied through a clinical trial process and made available only after proven effective.