Leukemia Stem Cells Microenvironment

The dynamic interactions between leukemic cells and bone marrow (BM) cells in the leukemia BM microenvironment regulate leukemia stem cell (LSC) properties including localization, self-renewal, differentiation, and proliferation. Recent research of normal and leukemia BM microenvironments has revealed several key components of specific niches that provide a sanctuary where subpopulations of leukemia cells evade chemotherapy-induced death and acquire a drug-resistant phenotype, as well as the molecular pathways critical for microenvironment/leukemia interactions. Although the biology of LSCs shares many similarities with that of normal hematopoietic stem cells (HSCs), LSCs are able to outcompete HSCs and hijack BM niches. Increasing evidence indicates that these niches fuel the growth of leukemia cells and contribute to therapeutic resistance and the metastatic potential of leukemia cells by shielding LSCs. Not only "microenvironment-induced oncogenesis," but also a "malignancy-induced microenvironment" have been proposed. In this chapter, the key components and regulation of BM niches in leukemic BM is described. In addition, metabolic changes in LSCs, which are currently a subject of intense investigation, will also be discussed to understand LSC survival.