Myeloproliferative Neoplasm: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC and David Li MD
April 14, 2026

Myeloproliferative neoplasms are a group of blood cancers in which the bone marrow — the soft tissue inside bones that makes blood cells — produces too many of one or more types of blood cells. Unlike cancers, where cells multiply rapidly and stop functioning, the cells in myeloproliferative neoplasms usually look and work relatively normally at first; the problem is that too many of them are made, and this overproduction builds up over time, causing symptoms and increasing the risk of complications. Most myeloproliferative neoplasms are driven by specific genetic changes that can be identified through testing. This article will help you understand the findings in your pathology report, what each term means, and why it matters for your care.

What are the symptoms of a myeloproliferative neoplasm?

Symptoms vary depending on the type of myeloproliferative neoplasm and which blood cells are overproduced. Some people are diagnosed after a routine blood test shows abnormal counts before any symptoms develop. When symptoms do occur, they are caused by the effects of too many blood cells, enlargement of the spleen or liver, or, in more advanced disease, the bone marrow’s decreasing ability to function normally.

Common symptoms across the group include fatigue, night sweats, unintentional weight loss, and a feeling of fullness or discomfort in the upper left abdomen caused by an enlarged spleen — a condition called splenomegaly. The spleen enlarges because it takes over some of the bone marrow’s blood cell production when the marrow becomes crowded or scarred, and because abnormal cells accumulate there. Many people experience itching, particularly after a warm shower or bath. This is called aquagenic pruritus and is especially common in polycythemia vera.

Abnormal clotting is a major risk in myeloproliferative neoplasms, particularly in polycythemia vera and essential thrombocythemia. Too many red blood cells or platelets can make the blood thicker and more prone to forming clots in blood vessels. This can lead to deep vein thrombosis, pulmonary embolism, stroke, or heart attack. Paradoxically, very high platelet counts can also cause bleeding in some situations because the excess platelets interfere with normal clotting.

In primary myelofibrosis and in the advanced phases of polycythemia vera or essential thrombocythemia, increasing bone marrow scarring reduces the marrow’s ability to produce normal blood cells, leading to anemia, low platelet counts, and susceptibility to infection — symptoms that resemble those of myelodysplastic syndrome or acute leukemia.

What causes myeloproliferative neoplasms?

Myeloproliferative neoplasms are caused by acquired mutations — changes in DNA that occur during a person’s lifetime in a single blood stem cell in the bone marrow. That stem cell then passes the mutation on to all the blood cells it produces, creating a large population of cells that all carry the same change. This is called a clonal disorder, meaning the abnormal cells all descend from one original abnormal cell.

The most important mutation in myeloproliferative neoplasms is in the JAK2 gene. The JAK2 gene encodes a protein that acts as a switch controlling blood cell production. Normally, this switch turns on when the body needs more blood cells and turns off when enough have been made. The most common mutation, called JAK2 V617F, permanently activates JAK2, causing the bone marrow to continuously overproduce blood cells even when the body does not need them. JAK2 V617F is found in nearly all people with polycythemia vera and in roughly half of those with essential thrombocythemia or primary myelofibrosis.

Two other mutations account for most of the remaining cases. Mutations in the CALR gene — which provides instructions for a protein involved in protein folding inside cells — are found in approximately 20–25% of people with essential thrombocythemia or primary myelofibrosis who do not have the JAK2 V617F mutation. Mutations in the MPL gene, which encodes the receptor for the hormone that stimulates platelet production, are found in approximately 3–5% of cases. In a small number of people with essential thrombocythemia or primary myelofibrosis, none of these three mutations is found; this is called triple-negative disease.

In the vast majority of people, these mutations arise by chance and are not inherited. Rarely, familial clustering occurs, and in those situations, genetic counseling may be recommended.

How is the diagnosis made?

The diagnosis of a myeloproliferative neoplasm is made by combining blood test results, bone marrow biopsy, and molecular genetic testing. A complete blood count often provides the first clue — showing elevated red blood cells, elevated platelets, elevated white blood cells, or some combination of these, depending on the type. A blood smear is examined under the microscope to assess cell appearance and identify any abnormal forms. The pathologist then evaluates a bone marrow biopsy and aspiration, looking at the overall cellularity of the marrow, the proportions of each cell type, and the appearance of megakaryocytes — the large bone marrow cells that produce platelets — which show characteristic abnormalities in each type of myeloproliferative neoplasm. The degree of bone marrow scarring, called fibrosis, is graded and recorded because it affects prognosis and treatment decisions. Molecular testing for JAK2, CALR, and MPL mutations is essential and is usually performed on blood, with bone marrow used if the blood result is inconclusive. Identifying which mutation is present helps confirm the specific type and guides both prognosis and treatment selection.

What are the types of myeloproliferative neoplasms?

The three main classic myeloproliferative neoplasms are polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Chronic myeloid leukemia is also a myeloproliferative neoplasm but is a distinct disease driven by a different mechanism — the BCR::ABL1 fusion gene — and is covered in its own article. The classic three share the same driver mutations (JAK2, CALR, MPL) and exist on a biological continuum, with polycythemia vera and essential thrombocythemia able to progress over time into secondary myelofibrosis or, rarely, into acute myeloid leukemia.

Polycythemia vera

In polycythemia vera, the bone marrow overproduces red blood cells, often alongside elevated white blood cells and platelets. The excess red blood cells make the blood thicker, significantly increasing the risk of blood clots. Nearly all people with polycythemia vera carry the JAK2 V617F mutation. Aquagenic pruritus — itching after warm water exposure — is a characteristic symptom. Under the microscope, the bone marrow is hypercellular (more cells than normal for the patient’s age) with expansion of all three blood cell types, a pattern called panmyelosis. Treatment focuses on reducing the risk of clotting through phlebotomy (regular blood removal), low-dose aspirin, and medications such as hydroxyurea or ruxolitinib. Long-term, approximately 20% of people develop post-polycythemia vera myelofibrosis, and a smaller proportion progress to acute myeloid leukemia.

Essential thrombocythemia

Essential thrombocythemia is characterized by a persistent high platelet count driven by overproduction of megakaryocytes in the bone marrow. Platelets above 450 × 10⁹/L that persist without another explanation are the hallmark finding. JAK2 V617F is present in roughly 50–60% of cases, CALR mutations in approximately 25%, and MPL mutations in around 3–5%. Under the microscope, megakaryocytes are increased in number, appear large and mature, and have deeply folded, staghorn-shaped nuclei — a characteristic appearance that helps distinguish essential thrombocythemia from other causes of high platelet counts. Bone marrow scarring is minimal at diagnosis. Essential thrombocythemia is the most favorable of the three classic MPNs; many people live for decades without significant complications. The main risks are blood clots and, in a minority, transformation to myelofibrosis or acute myeloid leukemia over many years.

Primary myelofibrosis

Primary myelofibrosis is the most aggressive of the three classic MPNs. It is characterized by progressive scarring of the bone marrow — the fibrosis — which gradually replaces normal blood-producing tissue. As the marrow scars, blood cell production shifts to the spleen and liver, causing significant enlargement of these organs. Blood counts are often abnormal in multiple directions simultaneously: some patients have elevated counts early, while others develop anemia and low platelet counts as the disease progresses. The blood smear shows a characteristic pattern called leukoerythroblastosis, with immature white blood cells and nucleated red blood cells circulating in the blood. Tear-drop-shaped red blood cells — called dacrocytes — are another hallmark finding. Under the microscope, the bone marrow shows increased and abnormal megakaryocytes forming dense clusters, alongside varying degrees of fibrosis graded on a scale from MF-0 (no fibrosis) to MF-3 (dense fibrosis with new bone formation). Primary myelofibrosis carries the worst prognosis of the three classic MPNs, with a median survival that varies widely by risk group. Allogeneic stem cell transplantation is the only potentially curative treatment.

Bone marrow fibrosis grading

The degree of scarring in the bone marrow is graded using a standardized system and is reported in bone marrow biopsy results for all three classic myeloproliferative neoplasms. Fibrosis grade matters because it affects prognosis and treatment decisions, particularly in primary myelofibrosis and in people with polycythemia vera or essential thrombocythemia who are being monitored for progression.

MF-0 — No fibrosis. The bone marrow has a normal network of fine fibers. This is typical of early essential thrombocythemia and polycythemia vera at diagnosis.
MF-1 — Mild fibrosis. There is a loose network of increased fibers with some crossing points. This may be seen in early primary myelofibrosis (called prefibrotic primary myelofibrosis) and in some cases of polycythemia vera or essential thrombocythemia.
MF-2 — Moderate fibrosis. Fibers are dense and diffuse with extensive crossing points but no areas of solid scarring. This indicates established fibrotic disease.
MF-3 — Severe fibrosis. Dense, coarse fibers with focal or diffuse areas of solid collagen and sometimes new bone formation (called osteosclerosis). This represents advanced myelofibrosis.

Higher fibrosis grades in primary myelofibrosis are associated with more severe symptoms, a greater degree of splenomegaly, and a higher risk of transformation to acute myeloid leukemia.

Biomarker and molecular testing

Molecular testing is essential in myeloproliferative neoplasms — both at diagnosis and during follow-up. The specific mutation found affects diagnosis, prognosis, and treatment selection.

JAK2 V617F mutation

JAK2 V617F is the defining mutation of polycythemia vera (present in ~97% of cases) and is also present in approximately 50–60% of essential thrombocythemia and primary myelofibrosis cases. The JAK2 protein normally functions as part of a signaling pathway that tells blood stem cells when to produce more cells in response to hormonal signals. The V617F mutation causes JAK2 to remain permanently active, continuously driving blood cell overproduction without waiting for a hormonal signal. In polycythemia vera, the allele burden — the percentage of JAK2-mutated cells — tends to be higher than in essential thrombocythemia and may be associated with a higher risk of progression and thrombosis. JAK2 V617F testing is performed on blood and is typically one of the first tests ordered when a myeloproliferative neoplasm is suspected.

JAK2 mutation status has direct treatment implications. JAK inhibitors — drugs that block the overactive JAK signaling pathway — are approved for myeloproliferative neoplasms. Ruxolitinib is approved for polycythemia vera that is inadequately controlled by or intolerant of hydroxyurea, and for intermediate- and high-risk primary myelofibrosis. It reduces spleen size, controls symptoms such as night sweats and itching, and improves quality of life in the majority of treated patients; in clinical trials, approximately 20–38% of patients achieved a 35% or greater reduction in spleen volume. Fedratinib is also approved for intermediate- and high-risk primary myelofibrosis in patients newly diagnosed or who have become resistant to or intolerant to ruxolitinib. Pacritinib is approved specifically for primary myelofibrosis patients with very low platelet counts (below 50 × 10⁹/L), a group who previously had few treatment options. Momelotinib is approved for patients with primary myelofibrosis who are anemic, as it addresses both the JAK-driven disease and the anemia through an additional mechanism.

CALR mutation

CALR mutations are found in approximately 20–25% of cases of essential thrombocythemia and primary myelofibrosis, almost exclusively in patients who are JAK2 V617F-negative. The CALR gene normally produces a protein called calreticulin that helps fold other proteins correctly inside cells. Mutations in CALR create an abnormal version of this protein that inappropriately activates the MPL receptor — the same receptor that responds to the platelet-stimulating hormone thrombopoietin — driving platelet and blood cell overproduction. CALR mutations are classified as type 1 (a deletion of 52 base pairs) or type 2 (an insertion of 5 base pairs), along with other less common variants. In primary myelofibrosis, type 1 CALR mutations are associated with a more favorable prognosis than JAK2 V617F or triple-negative status, while type 2 CALR mutations have an intermediate prognosis. CALR-mutated essential thrombocythemia is generally associated with a lower thrombosis risk than JAK2 V617F-positive disease, though the platelet count is often higher.

MPL mutation

MPL mutations occur in approximately 3–5% of cases of essential thrombocythemia and primary myelofibrosis, again most commonly in JAK2-negative patients. The MPL gene encodes the receptor for thrombopoietin — the hormone that signals the bone marrow to produce more platelets. Mutations in MPL permanently activate this receptor, signaling continuous platelet production. The most common mutations are W515L and W515K. MPL-mutated disease is generally managed similarly to JAK2- or CALR-mutated disease.

Mutation burden monitoring

In myeloproliferative neoplasms, molecular testing is not only used at diagnosis but also periodically during follow-up to monitor the allele burden — the proportion of blood cells carrying the driver mutation. A rising allele burden over time can signal disease progression and prompt a reassessment of treatment. In patients undergoing stem cell transplantation, a falling allele burden toward zero is an important indicator of successful engraftment and disease control. Your care team will advise on how frequently molecular monitoring is appropriate for your situation.

For more information about biomarkers and molecular testing in blood cancers, visit the Biomarkers and Genetic Testing section.

Risk stratification

Risk stratification in myeloproliferative neoplasms is used differently than in acute leukemia. In polycythemia vera and essential thrombocythemia, risk stratification focuses primarily on thrombosis risk—the likelihood of a dangerous blood clot—and is used to guide treatment intensity. In primary myelofibrosis, risk stratification predicts overall survival and is used to determine whether stem cell transplantation should be pursued.

In polycythemia vera and essential thrombocythemia, patients are classified as low risk or high risk based on age (over 60 is higher risk) and history of a prior thrombotic event. High-risk patients require cytoreductive therapy — medication to reduce blood cell counts — in addition to aspirin and, for polycythemia vera, phlebotomy. JAK2 V617F status, cardiovascular risk factors, and platelet count are also considered.

In primary myelofibrosis, several prognostic scoring systems exist. The most widely used is the Dynamic International Prognostic Scoring System Plus (DIPSS Plus), which incorporates age, symptoms, blood counts, blast percentage, transfusion need, platelet count, and cytogenetic findings to categorize patients as low, intermediate-1, intermediate-2, or high risk. Median survival ranges from over 15 years for low-risk disease to approximately 2 years for high-risk disease. High-molecular-risk mutations — particularly in genes such as ASXL1, SRSF2, EZH2, and IDH1/2 — are associated with worse outcomes and are increasingly incorporated into risk assessment. Patients with intermediate-2 or high-risk disease are generally considered for allogeneic stem cell transplantation if they are eligible.

Disease progression and transformation

One of the most important concepts for patients with myeloproliferative neoplasms is that these conditions exist on a spectrum and can change over time. Polycythemia vera and essential thrombocythemia, while initially indolent (slow-growing), can both transform into secondary myelofibrosis — a process called post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis, respectively. This happens in approximately 10–20% of people with polycythemia vera and 5–10% of people with essential thrombocythemia over ten or more years. Secondary myelofibrosis behaves similarly to primary myelofibrosis and is managed in the same way.

All three classic myeloproliferative neoplasms carry a risk of transformation into blast-phase disease, also called accelerated phase (10–19% blasts) or blast phase (20% or more blasts, equivalent to acute myeloid leukemia). This transformation is most common in primary myelofibrosis (approximately 10–20% of patients over ten years), less common in polycythemia vera (approximately 2–7%), and relatively rare in essential thrombocythemia (less than 2%). Blast phase transformation is a serious development that requires a different treatment approach, often including acute leukemia-type chemotherapy and consideration of stem cell transplantation. Acquisition of additional mutations — particularly in TP53 — is associated with an elevated risk of transformation.

What is the prognosis?

Prognosis varies significantly by type. Essential thrombocythemia has the most favorable outlook. Many people live for decades after diagnosis, and life expectancy for low-risk essential thrombocythemia approaches that of age-matched individuals without the disease. The main cause of morbidity and mortality is thrombosis rather than leukemic transformation.

Polycythemia vera has an intermediate prognosis. With treatment, many people live for 10–20 years or more after diagnosis. Thrombosis remains the primary risk. Transformation to secondary myelofibrosis or acute leukemia worsens the outlook significantly, but these events are not inevitable and often take many years to occur, if they occur at all.

Primary myelofibrosis has the most variable prognosis, ranging from more than 15 years for low-risk disease to approximately 2 years for high-risk disease. Allogeneic stem cell transplantation can be curative but carries significant risks of its own and is not appropriate for all patients. JAK inhibitors have substantially improved symptom control and quality of life but have not been shown to reliably prevent disease progression or extend survival in the way that transplantation can. Factors associated with a worse prognosis include older age, adverse cytogenetics, high-risk molecular mutations (ASXL1, SRSF2, EZH2, IDH1/2), high blast count, and need for transfusions.

Prognosis is best discussed with your hematologist, who can apply the relevant scoring system to your specific findings and give you the most accurate and individualized estimate.

What happens after the diagnosis?

After a myeloproliferative neoplasm is diagnosed, management depends on the specific type, risk category, and individual factors such as age and overall health. In lower-risk polycythemia vera and essential thrombocythemia, the initial focus is on reducing the risk of blood clots. Low-dose aspirin is typically recommended for most patients. For polycythemia vera, regular phlebotomy — removing blood to reduce the red cell mass and thin the blood — is often the first treatment. High-risk patients with either condition are started on cytoreductive therapy, most commonly hydroxyurea, to bring blood counts into the normal range and reduce the risk of clotting. Interferon-based therapies (such as ropeginterferon alfa-2b, approved for polycythemia vera) offer an alternative that may reduce the allele burden over time.

For primary myelofibrosis, patients with low- or intermediate-1-risk and minimal symptoms may be managed with watchful waiting and supportive care, including treatment of anemia if needed. Patients with intermediate-2 or high-risk disease, or those with significant symptoms, are typically offered a JAK inhibitor such as ruxolitinib, which reduces spleen size and improves constitutional symptoms in the majority of treated patients. Eligible patients with intermediate-2 or high-risk disease are referred for allogeneic stem cell transplantation evaluation.

All patients with myeloproliferative neoplasms require ongoing monitoring with regular blood counts and periodic bone marrow biopsies to assess for progression, increasing fibrosis, or blast transformation. Your care team will establish a follow-up schedule based on your specific type and risk category.

Questions to ask your doctor

Which type of myeloproliferative neoplasm do I have — polycythemia vera, essential thrombocythemia, or primary myelofibrosis?
What mutation was found — JAK2, CALR, MPL, or none — and what does that mean for my prognosis and treatment?
What is my risk category, and how does it affect treatment decisions?
What is the degree of bone marrow scarring (fibrosis grade), and what does that mean for how my disease may progress?
Am I at increased risk for blood clots, and what steps should I take to reduce that risk?
What treatment is recommended for me — phlebotomy, aspirin, cytoreductive therapy, or a JAK inhibitor — and why?
How will you monitor my disease over time, and how often will I need blood tests or bone marrow biopsies?
What signs or symptoms should prompt me to contact you between appointments?
Is my disease at risk of transforming to myelofibrosis or acute leukemia, and what would that change about my treatment?
Am I a candidate for a stem cell transplant, either now or in the future?
Are there clinical trials I should consider?
Could my mutation be related to an inherited condition that my family members should know about?