Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers in which excess red blood cells, white blood cellsorplatelets 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.
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.
People with MPNs might not have symptoms when their disease is first detected via blood tests.[6] Depending on the nature of the myeloproliferative neoplasm, diagnostic tests may include red cell mass determination (for polycythemia), bone marrow aspirate and trephine biopsy, arterial oxygen saturation and carboxyhaemoglobin level, neutrophil alkaline phosphatase level, vitamin B12 (or B12 binding capacity), serum urate[7] or direct sequencing of the patient's DNA.[8] According to WHO diagnostic criteria published in 2016, myeloproliferative neoplasms are diagnosed as follows:[9]
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.
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. Tyrosine kinase inhibitors like imatinib have improved the prognosis of CML patients to near-normal life expectancy.[14]
Recently, a JAK2 inhibitor, namely ruxolitinib, has been approved for use in primary myelofibrosis.[15] Trials of these inhibitors are in progress for the treatment of the other myeloproliferative neoplasms.
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]
The concept of myeloproliferative disease was first proposed in 1951 by the hematologistWilliam Dameshek.[18]
The discovery of the association of MPNs with the JAK2 gene marker in 2005 and the CALR marker in 2013 improved the ability to classify MPNs.[19]
MPNs were classified as blood cancers by the World Health Organization in 2008.[20] Previously, they were known as myeloproliferative diseases (MPD).
^Levene, Malcolm I.; Lewis, S. M.; Bain, Barbara J.; Imelda Bates (2001). Dacie & Lewis Practical Haematology. London: W B Saunders. p. 586. ISBN0-443-06377-X.
^Campbell PJ, Scott LM, Buck G, Wheatley K, East CL, Marsden JT, et al. (December 2005). "Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study". Lancet. 366 (9501): 1945–53. doi:10.1016/S0140-6736(05)67785-9. PMID16325696. S2CID36419846.