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

SIMPLE SUMMARY: Since the discovery of the role of the three driver mutations (JAK2, CALR and MPL) and the constitutive activation of the JAK/STAT pathway in myeloproliferative neoplasms, the disease has been wrongly considered to be molecularly elucidated, and efforts have mainly focused on the implementation of JAK inhibitors in the clinical setting. This review aims to bring together some of the most relevant studies addressing factors other than genetic alterations that may also play a role in the origin, evolution and progression of the disease and could, therefore, be the target of new therapies as well. 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.