Myeloproliferative neoplasm

Myeloproliferative neoplasm
Other names	Myeloproliferative diseases (MPDs)
Myelogram of someone with a myeloproliferative disorder.
Specialty	Hematology and oncology

Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers in which excess red blood cells, white blood cells or platelets are produced in the bone marrow. Myelo refers to the bone marrow, proliferative describes the rapid growth of blood cells and neoplasm describes that growth as abnormal and uncontrolled.

The overproduction of blood cells is often associated with a somatic mutation, for example in the JAK2, CALR, TET2, and MPL gene markers.

In rare cases, some MPNs such as primary myelofibrosis may accelerate and turn into acute myeloid leukemia.^[1]

Classification

MPNs are classified as blood cancers by most institutions and organizations.^[2] In MPNs, the neoplasm (abnormal growth) starts out as benign and can later become malignant.

As of 2016, the World Health Organization lists the following subcategories of MPNs:^[3]

• Chronic myeloid leukemia
  (CML)
• Chronic neutrophilic leukemia (CNL)
• Polycythemia vera (PV)
• Primary myelofibrosis (PMF)
  • PMF, prefibrotic stage
  • PMF, overt fibrotic stage
• Essential thrombocythemia (ET)
• Chronic eosinophilic leukemia (not otherwise specified)
• MPN, unclassifiable (MPN-U)

Causes

MPNs arise when

Chronic neutrophilic leukemia (CNL) is characterized by a mutation in the CSF3R gene and an exclusion of other causes of neutrophilia.

Essential thrombocythemia

Essential thrombocythemia (ET) is diagnosed with a platelet count greater than 450 × 109/L and is associated with the JAK2 V617F mutation in up to 55% of cases^[10] and with an MPL (thrombopoietin receptor) mutation in up to 5% of cases:.^[11] There should be no increase in reticulin fibers and the patient should not meet the criteria for other MPNs, in particular Pre-PMF.

Polycythemia vera

Polycythemia vera (PV) is associated most often with the JAK2 V617F mutation greater than 95% of cases, whereas the remainder has a JAK2 exon 12 mutations. High hemoglobin or hematocrit counts are required, as is a bone marrow examination showing "prominent erythroid, granulocytic and megakaryocytic proliferation with pleomorphic, mature megakaryocytes."

Prefibrotic/early primary myelofibrosis

Prefibrotic primary myelofibrosis (Pre-PMF) is typically associated with JAK2, CALR, or MPL mutations and shows reticulin fibrosis no greater than grade 1. Anemia, splenomegaly, LDH above the upper limits and leukocytosis are minor criteria.^[12]

Overtly fibrotic myelofibrosis

Like

No curative drug treatment exists for MPNs.[13] Hematopoietic stem cell transplantation can be a curative treatment for a small group of patients, however MPN treatment is typically focused on symptom control and myelosuppressive drugs to help control the production of blood cells.^{[citation needed]}

The goal of treatment for ET and PV is prevention of thrombohemorrhagic complications. The goal of treatment for MF is amelioration of anemia, splenomegaly, and other symptoms. Low-dose aspirin is effective in PV and ET.

Although considered rare diseases, incidence rates of MPNs are increasing, in some cases tripling. It is hypothesized that the increase may be related to improved diagnostic abilities from the identification of the JAK2 and other gene markers, as well as continued refinement of the WHO guidelines.^[16]

There is wide variation in reported MPN incidence and prevalence worldwide, with a publication bias suspected for essential thrombocythemia and primary myelofibrosis.^[17]

History

The concept of myeloproliferative disease was first proposed in 1951 by the

MPNs were classified as blood cancers by the World Health Organization in 2008.^[20] Previously, they were known as myeloproliferative diseases (MPD).

In 2016, Mastocytosis was no longer classified as an MPN.^[21]

References