Distinct Stromal Cell Populations Define the B-cell Acute Lymphoblastic Leukemia Microenvironment

The bone marrow microenvironment is critical for B-cell acute lymphoblastic leukemia (B-ALL) but its cellular heterogeneity remains poorly defined. Here, we employed single-cell RNA sequencing to comprehensively characterize the stromal and hematopoietic niches in pediatric B-ALL. Our analysis revealed two distinct mesenchymal stromal cell (MSC) populations as primary leukemia-supportive niches: early mesenchymal progenitors and adipogenic progenitors. Single-cell transcriptomic analysis infers that ALL blasts use distinct cell-cell interactions to communicate with the different stromal populations. Purified adipogenic progenitors from the bone of children with ALL support survival of the leukemic blasts ex vivo and their signature is enriched in relapse samples. Our data establish adipogenic progenitors as a distinct and novel component of the ALL niche.