The hematopoietic stem-cell niche in health and leukemia

Abstract

Research in the last decade has shown that hematopoietic stem cells (HSCs) interact with and are modulated by a complex multicellular microenvironment in the bone marrow, which includes both the HSC progeny and multiple non-hematopoietic cell types. Intense work is gradually throwing light on the composition of the HSC niche and the molecular cues exchanged between its components, which has implications for HSC production, maintenance and expansion. In addition, it has become apparent that bidirectional interactions between leukemic cells and their niche play a previously unrecognized role in the initiation and development of hematological malignancies. Consequently, targeting of the malignant niche holds considerable promise for more specific antileukemic therapies. Here we summarize the latest insights into HSC niche biology and recent work showing multiple connections between hematological malignancy and alterations in the bone marrow microenvironment.

Keywords: Bone marrow microenvironment; Hematopoietic stem cell; Leukemia; Leukemia stem cell; Stem cell niche.

Fig. 1

Overview of the main components of the HSC niche and their alterations in leukemia. Simplified schematic of the normal HSC niche (left) and its alterations in the context of malignancy. The diagram does not attempt to comprehensively include every cell population and molecule implicated in HSC regulation but to illustrate some of the best characterized candidate niche cells and factors, particularly those that have been found altered in leukemias. The right panel summarizes niche abnormalities observed in various experimental models representing different leukemia types. Therefore, it does not intend to propose a general model nor to describe the pathophysiology of any particular malignancy. HSC hematopoietic stem cell, LSC leukemia stem/initiating cell