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.

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