What is a myeloproliferative neoplasm?

Myeloproliferative neoplasm (MPN) is used to describe a class of chronic hematologic disorders in which there is abnormal production of blood cells by stem cells in the bone marrow. The name is derived from the combination of the Greek word, myelos, which means marrow, proliferative, which means growing or reproducing rapidly, and neoplasm, derived from combining the Greek terms neo, meaning new, and plasma, which means formation.

Bone marrow is the organ in the body in which blood is formed. Formation of blood is called hematopoiesis. The bone marrow contains blood-forming stem cells called pluripotent hematopoietic precursor cells (PHPC), which have two important functions: (1) self-renewal, to maintain a pool of stem cells for future proliferation or growth, and (2) the ability to mature into adult blood cells that will leave the bone marrow and enter the blood. Each PHPC can reproduce (or clone) itself, as well as produce a number of immature daughter cells, called blasts.

Normal bone marrow is composed of a family of hematopoietic clones, all reproducing themselves and forming specific types of daughter cells, with each type dedicated to developing into either a red blood cell (RBC), white blood cell (WBC), or platelet. The dedicated daughter cells divide over and over again, and it is their growth that fills the marrow with the diverse types of immature and developing blood cells that are seen in a normal bone marrow specimen. The normal marrow also balances production of different cell types so they appear in the blood in their proper proportions.

In MPN, one abnormal PHPC clone has a growth advantage that allows it to reproduce more aggressively than the normal stem cells, and eventually these abnormal clones take over the marrow. Although this PHPC clone is "abnormal," it is still able to self-renew and to produce several types of immature blood cells that may be difficult to distinguish from those produced by normal cells. In MPN, there is abnormal overproduction or underproduction of a particular cell type. Thus, MPN involves an improper balance in the production of different blood cell types, as well as abnormal production of any given blood cell type.

Chronic myeloid leukemia (CML) is an MPN that results in a great overproduction of WBCs. CML is characterized by the presence of a chromosomal abnormality known as the Philadelphia chromosome. MPNs in which this abnormality is absent are known collectively as Philadelphia-chromosome-negative MPNs, and the three most common of these are the classic MPNs: primary myelofibrosis (PMF), in which impaired production of RBCs, and sometimes other cells, is present; polycythemia vera (PV), in which there is an overproduction of RBCs and sometimes other cells; and essential thrombocythemia (ET), in which there is an overproduction of platelets.

Genetic studies indicate the appearance of the abnormal stem cells in a patient diagnosed with MPN is due to a mutation in a gene, known as an acquired mutation (that is, the mutation is not present at birth). It is not understood currently what triggers the mutation to occur. In the Philadelphia-chromosome-negative MPNs, the most common mutation is on the Janus kinase 2 (JAK2) gene, and is called V617F. The JAK2 V617F mutation is present in more than 50% of patients with PMF and ET and more than 95% of patients with PV.1,2 Testing for the presence of the JAK2 V617F mutation has been incorporated into diagnostic testing for MPNs. Other mutations on JAK2 or on other genes may be present in patients with or without the V617F mutation, but limited testing for these mutations is currently available.


  1. Tefferi A, Vainchenker W. Myeloproliferative neoplasms: Molecular pathophysiology, essential clinical understanding, and treatment strategies. J Clin Oncol. 2011;29(5):573-582.
  2. Tefferi A. Myeloproliferative neoplasms 2012: The John M. Bennett 80th birthday anniversary lecture. Leukemia Research. 2012;36:1481-1489.