Bone marrow niche and leukemia.

Abstract

Mounting evidence indicates that human cancers may originate from malignant transformation of stem cells. The most convincing proof is found in acute myeloid leukemia, where only a small subset of slowly dividing cells was able to induce transplantable acute myeloid leukemia. Normal hematopoietic stem cells (HSC) are characterized by their unlimited ability to self-renew, give rise to a multitude of cells that exhibit more differentiated features, and show slow division kinetics. Using human HSC and mesenchymal stromal cells (MSC) as models, we and others have demonstrated the vital role of the cellular niche in maintaining the self-renewing capacity, that is, "stemness" of HSC. Without direct contact with the cellular niche, HSC tend to differentiate and lose their stemness. Similar to their normal counterparts, leukemia stem cells divide slowly and maintain their self-renewal capacity through interaction with the niche. As a consequence, they are resistant to conventional chemotherapy strategies that target rapidly dividing cells. Thus it is of utmost importance to understand the interaction between cellular niche and normal HSC as well as between leukemia stem cells and the niche to provide a basis for more efficient treatment strategies.