The Hematopoietic Microenvironment in Myeloproliferative Neoplasms: The Interplay Between Nature (Stem Cells) and Nurture (the Niche).

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.