Mapping and targeting of the leukemic microenvironment

Abstract

Numerous studies support a role of the microenvironment in maintenance of the leukemic clone, as well as in treatment resistance. It is clear that disruption of the normal bone marrow microenvironment is sufficient to promote leukemic transformation and survival in both a cell autonomous and non-cell autonomous manner. In this review, we provide a snapshot of the various cell types shown to contribute to the leukemic microenvironment as well as treatment resistance. Several of these studies suggest that leukemic blasts occupy specific cellular and biochemical "niches." Effective dissection of critical leukemic niche components using single-cell approaches has allowed a more precise and extensive characterization of complexity that underpins both the healthy and malignant bone marrow microenvironment. Knowledge gained from these observations can have an important impact in the development of microenvironment-directed targeted approaches aimed at mitigating disease relapse.

Figure 1.

Dynamic interactions between leukemic blasts and their niche. Schematic depicts the multiple extrinsic regulatory mechanisms implicated in promoting leukemic blast survival, highlighting critical interactions that either promote (blue) or inhibit (red) leukemic cell growth. Upon disease transformation, remodeling of the leukemic bone marrow microenvironment involves various interactions between leukemia and its microenvironment that may be reciprocal and multifaceted. Non-hematopoietic components (such as osteolineage cells, adipose tissue, and mesenchymal and vascular endothelial cells), the immune microenvironment, and the sympathetic nervous system have all been previously implicated in cell-mediated regulation on leukemic survival.