The Hematopoietic Microenvironment in Myeloproliferative Neoplasms: The Interplay Between Nature (Stem Cells) and Nurtur
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-int
- PDF / 342,796 Bytes
- 11 Pages / 504.567 x 720 pts Page_size
- 106 Downloads / 200 Views
The Hematopoietic Microenvironment in Myeloproliferative Neoplasms: The Interplay Between Nature (Stem Cells) and Nurture (the Niche) Huichun Zhan and Kenneth Kaushansky
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
H. Zhan (*) Division of Hematology-Oncology, Department of Medicine, Stony Brook School of Medicine, Stony Brook, NY, USA Northport VA Medical Center, Northport, NY, USA e-mail: [email protected]; [email protected] K. Kaushansky (*) Stony Brook School of Medicine, Stony Brook, NY, USA e-mail: [email protected]
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. Keywords
Myeloproliferative neoplasm · Polycythemia vera · Essential thrombocythemia · Primary myelofibrosis · JAK2V617F · Hematopoiesis · Hematopoietic stem cell · Microenvironment · Vascular niche · Endothelial cell · Megakaryocyte · Clonal expansion · Radioprotection · Thrombopoietin · MPL
7.1
The Hematopoietic Microenvironment
The hematopoietic microenvironment or “stem cell niche” is defined as the site at which HSCs reside and are nurtured, receiving the humoral
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2020 A. Birbrair (ed.), Tumor Microenvironment, Advances in Experimental Medicine and Biology 1273, https://doi.org/10.1007/978-3-030-49270-0_7
135
H. Zhan and K. Kaushansky
136
and cell-surface signals that lead to their survival, replication, and/or differentiation into all the mature cells of the blood. Technical breakthroughs in imaging HSCs in the marrow cavity, coupled with a series of elegant functional studies in murine models, have identified a number of HSC niche cells that provide the secreted factors and cell-surface molecules essential for HSC maintenance and function. The cellular components of the marrow HSC niche are derived from both hematopoietic and non-hematopoietic cells. Examples of non-hematopoietic niche cells are perivascular stromal cells and endothelial cells (ECs),
Data Loading...
