Introduction to a review series on myeloproliferative neoplasms.

According toPubMed, the adjective“myeloproliferative”wasused for the first time in the title of a scientific paper by William Dameshek in 1951, when he published an editorial in Blood entitled, “Some speculations on the myeloproliferative syndromes.” In this article, featured in the recent Blood Flashback series, Dameshek introduced the concept of myeloproliferative disorders as conditions characterized by excessive proliferation of hematopoietic precursors in the bonemarrow and excessive production of mature blood cells. He included in this category chronic granulocytic leukemia, polycythemia vera (PV), idiopathic or agnogenic myeloid metaplasia of spleen, megakaryocytic leukemia, and erythroleukemia. Although some of these names are no longer in use, Dameshek’s editorial represents a remarkable example of visionary leadership. In2008, tounderscore theclonalnatureofmyeloproliferativedisorders, the authors of theWHOClassification of Tumours of Haematopoietic and Lymphoid Tissues introduced the name “myeloproliferative neoplasms” (MPNs). The revised version of this classification includes the following MPNs: chronic myeloid leukemia (CML), BCR-ABL1; chronic neutrophilic leukemia (CNL); PV; primarymyelofibrosis (PMF); essential thrombocythemia (ET); chronic eosinophilic leukemia, not otherwise specified; and MPN, unclassifiable. In addition, the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues comprises the myeloid/lymphoid neoplasms with eosinophilia and rearrangements of PDGFRA, PDGFRB, FGFR1, or with PCM1-JAK2. Over recent years, there have been tremendous advances in our understanding of the genetic basis of MPNs and related myeloid neoplasms. Milestones in this field include the following discoveries: (1) the FIP1L1-PDGFRA fusion gene in patients with hypereosinophilic syndrome in 2003; (2) the unique JAK2 (V617F) mutation in patients with classical MPNs in 2005; (3) oncogenic CSF3R mutations in patients with CNL in 2013; and (4) somatic mutations of CALR in classical MPNs in 2013. The following series of reviews describes the latest advances in our understanding of the genetic basis of MPNs and related myeloid neoplasms, as well as of its clinical relevance: