Abstract
Hematopoietic stem cells (HSCs) rely on instructive cues from the marrow microenvironment for their maintenance and function. Accumulating evidence indicates that the survival and proliferation of hematopoietic neoplasms are dependent not only on cell-intrinsic, genetic mutations, and other molecular alterations present within neoplastic stem cells, but also on the ability of the surrounding microenvironmental cells to nurture and promote the malignancy. It is anticipated that a better understanding of the molecular and cellular events responsible for these microenvironmental features of neoplastic hematopoiesis will lead to improved treatment for patients. This review will focus on the myeloproliferative neoplasms (MPNs), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), in which an acquired signaling kinase mutation (JAK2V617F) plays a central, pathogenetic role in 50–100% of patients with these disorders. Evidence is presented that the development of an MPN requires both an abnormal, mutation-bearing (i.e., neoplastic) HSC and an abnormal, mutation-bearing microenvironment.
Original language | English |
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Title of host publication | Advances in Experimental Medicine and Biology |
Publisher | Springer |
Pages | 135-145 |
Number of pages | 11 |
DOIs | |
State | Published - 2020 |
Externally published | Yes |
Publication series
Name | Advances in Experimental Medicine and Biology |
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Volume | 1273 |
ISSN (Print) | 0065-2598 |
ISSN (Electronic) | 2214-8019 |
Bibliographical note
Publisher Copyright:© 2020, The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG.
Keywords
- Clonal expansion
- Endothelial cell
- Essential thrombocythemia
- Hematopoiesis
- Hematopoietic stem cell
- JAK2V617F
- Megakaryocyte
- Microenvironment
- MPL
- Myeloproliferative neoplasm
- Polycythemia vera
- Primary myelofibrosis
- Radioprotection
- Thrombopoietin
- Vascular niche