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Pathophysiology of Myeloproliferative Neoplasms (MPNs)

MPNs develop when a series of acquired genetic mutations take place within the bone marrow compartment leading to a proliferation of clones of abnormal stem cells. Under normal circumstances, the bone marrow only produces the number of cells needed to replace old or dead cells so that relatively consistent levels of cellular concentrations are maintained. The genetic changes that occur allow the affected stem cells to multiply without appropriate regulation and control. This rise in abnormal cell production starts to hinder the production of normally functioning cells. Eventually, the abnormal clones overpower normal hematopoietic cell production until there are very few non-clonal cells being produced. Eventually as very few non-clonal cells are produced, the disease officially progresses into the classification of acute leukemia. The leukemia cells can spread outside the blood to other parts of the body, including the skin, brain, gums, etc.

Investigating the clonality of the cells can aid in the diagnosis of an MPN. Glucose-6-phosphate dehydrogenase (G6PD) enzyme is commonly used for this purpose. Since the commitment, differentiation, and maturation of the abnormal clone are still intact, a large population of mature cells derived from the stem cell clone are released into the peripheral blood, leading to increases in all cell populations. However, one of the cell lines always predominates (erythroid, myeloid, or megakaryocytic). MPNs with corresponding predominating cell lines are listed in the table below.

Myeloproliferative Neoplasm

Most Affected Cell Line

Chronic myelogenous leukemia


Chronic neutrophilic leukemia


Chronic eosinophilic leukemia


Essential thrombocythemia


Primary myelofibrosis


Polycythemia vera



Mast cell

Myeloproliferative neoplasm, unclassifiable

Inconsistent; varies