Myelofibrosis is a rare, chronic blood cancer in which the bone marrow slowly fills with scar tissue (fibrosis), so it can no longer make enough normal blood cells. People often call it “myelofibrosis leukemia,” and it is a close relative of leukemia. Strictly speaking, though, it is classified as a myeloproliferative neoplasm (MPN) rather than a leukemia, and it can occasionally turn into acute leukemia. It is caused by acquired mutations, most often in the JAK2, CALR or MPL genes. Diagnosis rests on a bone marrow biopsy, and treatment ranges from watchful monitoring to JAK inhibitor drugs and, for some patients, a stem cell transplant.
What Myelofibrosis Is, and How It Relates to Leukemia
Myelofibrosis belongs to the wider group of hematologic malignancies. It starts in a single blood-forming stem cell that picks up a mutation. That abnormal clone then expands and releases signaling molecules (cytokines) that stimulate fibroblasts, the cells that lay down scar tissue.
Healthy bone marrow is a soft, spongy tissue that makes red cells, white cells and platelets. As fibrosis builds up, blood production fails inside the bone and moves to the spleen and liver. This is called extramedullary hematopoiesis, and it is why the spleen can become very large.
There are two main forms:
- Primary myelofibrosis: the disease appears on its own.
- Secondary (post-PV or post-ET) myelofibrosis: it develops years after another MPN, either polycythemia vera or essential thrombocythemia.
Its link to leukemia comes from the risk that, in a minority of patients, the disease transforms into acute myeloid leukemia (AML). This is sometimes called the blast phase.
Causes and Risk Factors
Myelofibrosis is not inherited in the usual sense, and it is not contagious. The driver mutations are acquired during life. The three main ones are:
| Driver mutation | What it does | Clinical note |
|---|---|---|
| JAK2 (usually V617F) | Leaves the JAK-STAT growth signal permanently switched on | The most common driver; also found in polycythemia vera and essential thrombocythemia |
| CALR | An altered calreticulin protein activates the thrombopoietin receptor | The second most common driver |
| MPL | Directly activates the thrombopoietin receptor | Less common |
| None of the three (“triple-negative”) | Driver not yet identified | Generally linked to a less favorable outlook |
Recognized risk factors include older age (most patients are diagnosed in their 60s or later), a previous MPN, and exposure to high doses of radiation or to benzene. A family history of MPNs raises risk slightly. In most people, though, no clear trigger is ever found.
Signs and Symptoms
Early myelofibrosis may cause no symptoms and may be picked up only because a routine blood count is abnormal. As the disease progresses, typical features include:
- Fatigue and breathlessness from anemia, often the main problem for patients
- An enlarged spleen (splenomegaly), causing fullness under the left ribs, feeling full quickly, or left-sided pain
- Constitutional symptoms: night sweats, fevers, unintended weight loss and itching
- Bone or joint pain, and sometimes gout from rapid cell turnover
- Bruising, bleeding or infections when platelet or white cell counts drop
How Myelofibrosis Is Diagnosed
Diagnosis combines blood tests, a marrow biopsy and genetic testing, and is assessed against World Health Organization criteria.
- Complete blood count: anemia is common. White cells and platelets may be high early in the disease and low later on.
- Blood smear: a leukoerythroblastic picture (immature red and white cells in the bloodstream) and teardrop-shaped red cells (dacrocytes) are classic clues.
- Bone marrow biopsy: often a “dry tap,” because fluid cannot be drawn from the scarred marrow. The core biopsy shows abnormal megakaryocytes and reticulin or collagen fibrosis, which is graded on the European consensus scale from MF-0 to MF-3. Our article on bone marrow fibrosis explains this grading and the other causes of scarring.
- Molecular testing: looks for JAK2, CALR and MPL mutations, often alongside a wider gene panel that helps estimate risk.
- Other tests: a raised LDH and imaging of the spleen by ultrasound or MRI.
Doctors also have to rule out other causes of marrow fibrosis, such as other blood cancers, infections and autoimmune disease, before confirming primary myelofibrosis.
Treatment Options
Treatment depends on the patient’s risk category and on which symptoms bother them most. Hematologists estimate risk with prognostic scoring systems (such as DIPSS and MIPSS70) that combine age, blood counts, symptoms, blast percentage and genetic findings.
Observation
Lower-risk patients without troublesome symptoms may simply be monitored with regular blood counts and clinic visits.
JAK inhibitors
Ruxolitinib was the first JAK inhibitor approved for myelofibrosis. It shrinks the spleen and eases night sweats, itching and fatigue. Fedratinib, pacritinib and momelotinib are now also used, and the choice between them depends partly on platelet count and anemia. These drugs relieve symptoms well but do not cure the disease.
Managing anemia and counts
Options include red cell transfusions, erythropoiesis-stimulating agents, androgens or other anemia-directed drugs. Hydroxyurea may be used when white cell or platelet counts are too high, or to reduce spleen size.
Allogeneic stem cell transplant
A transplant from a donor is currently the only treatment with curative potential. It carries significant risks, so it is generally offered to fitter patients with intermediate- or high-risk disease.
Outlook and Recent Developments
The outlook varies widely. Some lower-risk patients live for many years with few problems, while higher-risk disease can progress over a shorter period. Your hematologist’s risk score gives the most personal estimate.
Research is aimed at drugs that target the fibrosis itself, combinations with JAK inhibitors, and better treatment for anemia. Gene sequencing now plays a routine part in deciding who should be referred for transplant.
Key Takeaways
- Myelofibrosis is a myeloproliferative neoplasm that scars the marrow; it is often called myelofibrosis leukemia and can transform into AML.
- Acquired JAK2, CALR or MPL mutations drive most cases.
- Anemia, an enlarged spleen and night sweats or weight loss are the classic features.
- A bone marrow biopsy with fibrosis grading and mutation testing confirms the diagnosis.
- JAK inhibitors control symptoms; a stem cell transplant is the only potential cure.
Frequently Asked Questions
Is myelofibrosis a type of leukemia?
Not strictly. It is a chronic myeloproliferative neoplasm, a blood cancer related to leukemia. It can progress to acute myeloid leukemia in some patients, which is why the two terms are often linked.
Is myelofibrosis hereditary?
The driver mutations are acquired during life rather than passed from parent to child. Relatives of people with MPNs have a slightly higher risk, but routine family screening is not usually recommended.
Why is the spleen so large in myelofibrosis?
As the marrow scars, blood-forming cells settle in the spleen and liver and start making blood there. This extramedullary hematopoiesis, together with the abnormal clone itself, enlarges the spleen, sometimes greatly.
Can myelofibrosis be cured?
Only an allogeneic stem cell transplant offers the possibility of cure. Other treatments, including JAK inhibitors, control symptoms and blood counts and can improve quality of life. More detail on the marrow itself is in our bone marrow guide.
