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Microenvironmental regulation of hematopoietic stem cells and its implications in leukemogenesis

Seshadri, Madhav; Qu, Cheng-Kui

Current Opinion in Hematology: July 2016 - Volume 23 - Issue 4 - p 339–345
doi: 10.1097/MOH.0000000000000251
HEMATOPOIESIS: Edited by Hal E. Broxmeyer

Purpose of review Hematopoietic stem cells (HSCs) are a population of cells in the bone marrow which can self-renew, differentiate into late lineage progenitors, or remain quiescent. HSCs exist alongside several cell types in the bone marrow microenvironment that comprise the stem cell niche. These cells regulate HSC function and can contribute to leukemogenesis. In this review we will discuss recent advances in this field.

Recent findings In the vascular niche, arteriolar and sinusoidal zones appear to play distinct roles in HSC function. Endothelial cells modulate HSC function via Notch and other signaling pathways. In the endosteal niche multiple cell types regulate HSCs. Osteoblasts promote HSC quiescence via secreted factors and possibly physical interactions, whereas adipocytes may oppose HSC quiescence. The balance of these opposing factors depends on metabolic cues. Feedback from HSC-derived cells, including macrophages and megakaryocytes also appears to regulate HSC quiescence. Dysfunction of the bone marrow microenvironment, including mesenchymal stem cell-derived stromal cells and the sympathetic nervous system can induce or alter the progression of hematologic malignancies.

Summary Many cell types in the bone marrow microenvironment affect HSC function and contribute to malignancy. Further understanding how HSCs are regulated by the microenvironment has clinical implications for stem cell transplantation and other therapies for hematologic malignancies.

Department of Pediatrics, Division of Hematology and Oncology, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA

Correspondence to Cheng-Kui Qu, MD, PhD, Division of Hematology/Oncology Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, 1760 Haygood Drive NE, HSRB E302 Atlanta, GA 30322, USA. E-mail:

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