Hematopoiesis and microenvironment in hematological malignancies

Abstract

Adult hematopoietic stem cells (HSCs) and progenitors (HPCs) reside in the bone marrow, a highly orchestrated architecture. In the bone marrow, the process of how HSCs exert self-renewal and differentiation is tightly regulated by the surrounding microenvironment, or niche. Recent advances in imaging technologies and numerous knockout or knockin mouse models have greatly improved our understanding of the organization of the bone marrow niche. This niche compartment includes a complex network of mesenchymal stem cells (MSC), osteolineage cells, endothelial cells (arterioles and sinusoids), sympathetic nerves, nonmyelinating Schwann cells and megakaryocytes. In addition, different types of mediators, such as cytokines/chemokines, reactive oxygen species (ROS) and exosomes play a pivotal role in regulating the function of hematopoietic cells. Therefore, the niche components and the hematopoietic system make up an ecological environment that maintains the homeostasis and responds to stress, damage or disease conditions. On the other hand, the niche compartment can become a traitor that can do harm to normal hematopoietic cells under pathological conditions. Studies on the diseased bone marrow niche have only recently begun to appear in the extant literature. In this short review, we discuss the most recent advances regarding the behaviors of normal hematopoietic cells and their niche alterations in hematological malignancies.

Keywords: Hematological malignancies; Hematopoietic progenitor cells; Hematopoietic stem cells; Leukemia; Microenvironment; Niche.

Fig. 1

Mechanisms for the suppression of normal hematopoiesis and niche in malignancies. A. Overview of the main components of the hematopoietic stem cell (HSC) niche in homeostasis. B. In malignant condition, normal HSCs are forced into a more quiescent state, and their differentiation is blocked. Malignant cells secrete soluble factors to suppress HSC function, partially due to several signaling pathways. C. Summaries of niche abnormalities observed in various models. Malignant cells remodel niche cells to create a self-reinforcing leukemic niche, which favors leukemic cell growth while suppressing normal hematopoiesis.