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Chronic myeloproliferative neoplasms

Are polycythemia vera, essential thrombocytosis, and primary myelofibrosis 1, 2, or 3 diseases?

Leukemia volume 35, pages 1890–1893 (2021)Cite this article

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The myeloproliferative neoplasms (MPNs), polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF) are unique clonal hematopoietic stem cell (HSC) neoplasms because their driver mutations promote the uncontrolled production of morphologically and functionally normal myeloid cells. Therefore, in contrast to other myeloid neoplasms, life span with supportive therapy alone is measured in decades rather than years in PV and ET, though in PMF, the life span is much shorter. Also in contrast to other myeloid neoplasms, because all MPN driver mutations activate the JAK2-STAT pathway, albeit by different mechanisms, PV, ET, and PMF display phenotypic mimicry among themselves as well as with certain benign and malignant hematologic disorders, making it difficult to identify the three MPNs clinically.

The discovery of JAK2 V617F in 2005 provided not only a genetic basis for MPN pathophysiology but also a means of distinguishing approximately 65% of MPN patients from patients with the benign blood disorders and hematologic malignancies they mimic. With the subsequent discovery of MPN driver mutations in the thrombopoietin receptor (MPL) and calreticulin (CALR) genes, it is now possible to genetically distinguish ≥95% of MPN patients from patients with the benign or malignant blood disorders they mimic.

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Fig. 1: The hematopoietic stem cell hierarchy.
Fig. 2: HSC gene expression differs between PV and ET.
Fig. 3: The clonal behavior of ET, PV, and PMF HSCs.

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  1. Division of Hematology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jerry L. Spivak

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Correspondence to Jerry L. Spivak.

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Spivak, J.L. Are polycythemia vera, essential thrombocytosis, and primary myelofibrosis 1, 2, or 3 diseases?. Leukemia 35, 1890–1893 (2021). https://doi.org/10.1038/s41375-021-01254-w

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