Targeting the leukemia-stroma interaction in acute myeloid leukemia: Rationale and latest evidence

The concept of niche' has become a focus of attention in hematologic malignancies including acute myeloid leukemia (AML). Similar to normal hematopoietic stem cells, AML cells interact both anatomically and functionally with the stroma within the marrow microenvironment. These interactions have a critical role in the development, progression, and relapse of AML. Chemotherapy resistance is another feature that is at least partially related to AML-stroma interactions. The evidence for safety and efficacy of agents targeting AML-niche interactions is currently limited to preclinical and early phase clinical studies. Examples include CXCR4 inhibitors, hypoxia-inducible agents, and adhesion molecule inhibitors. Agents that target AML-stroma interactions differ from mutation-specific approaches that tend to be limited due to within-individual and between-individual genetic heterogeneity. These agents may be used alone or as chemosensitizers in AML. This novel and rapidly advancing strategy is likely to become an important part of our armamentarium of anti-leukemia treatments in the near future.