Deepening Our Understanding of the Factors Affecting Landscape of Myeloproliferative Neoplasms: What Do We Know about Them?

Abstract

Myeloproliferative neoplasms (MPNs) arise from the uncontrolled proliferation of hematopoietic stem and progenitor cells in bone marrow. As with all tumors, the development of MPNs is a consequence of alterations in malignant cells and their interaction with other extrinsic factors that support and promote tumor progression. Since the discovery of driver mutations, much work has focused on studying and reviewing the genomic features of the disease but has neglected to delve into the important role that many other mechanisms may play. This review discusses the genetic component of MPNs but focuses mainly on some of the most relevant work investigating other non-genetic factors that may be crucial for the disease. The studies summarized here address MPN cell-intrinsic or -extrinsic factors and the interaction between them through transcriptomic, proteomic and microbiota studies, among others.

Case report: Effectiveness of low-dose methotrexate monotherapy in post-essential thrombocythemia myelofibrosis

“…JAK/STAT pathway signalling is central to multiple biological processes including inflammation, haematopoiesis and regulation of the immune system ( 1 ). Ectopic pathway activation is also associated with both chronic inflammatory conditions such as rheumatoid arthritis and psoriasis, as well as the chronic myeloid cancers collectively termed myeloproliferative neoplasms (MPNs) ( 2 ). MPNs include essential thrombocythemia (ET), associated with increased platelet counts, polycythemia vera (PV) associated with increased erythrocytes and myelofibrosis where bone marrow is replaced by fibrotic scar tissue—a condition that can be both a primary disease and a secondary development following ET or PV.…”

“…MPNs include essential thrombocythemia (ET), associated with increased platelet counts, polycythemia vera (PV) associated with increased erythrocytes and myelofibrosis where bone marrow is replaced by fibrotic scar tissue—a condition that can be both a primary disease and a secondary development following ET or PV. In all cases, MPNs are associated with increased JAK/STAT pathway activity driven by gain-of-function mutations such as JAK2 V617F, indel mutations resulting in a +1 frameshift affecting the C-terminal of Calreticulin or activating mutations adjacent to the transmembrane region of the thrombopoietin receptor MPL W515L/K [reviewed in Morales et al ( 2 )].…”