Adipocyte progenitors – a new player in the microenvironment of acute lymphoblastic leukemia
The bone marrow microenvironment is critical for B-cell acute lymphoblastic leukemia (B-ALL) progression, but its cellular heterogeneity remains poorly defined.
We isolated leukemic, hematopoietic, and stromal cells from mononuclear cells in patient samples using fluorescence-activated cell sorting. To comprehensively characterize the bone marrow niche in pediatric B-ALL, we conducted single-cell RNA sequencing and ex vivo cell culture.
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 marrow of pediatric B-ALL patients supported leukemic blasts survival ex vivo and their gene signature was enriched in relapse samples.
These findings establish adipogenic progenitors as a novel component of the ALL niche, with potential implications for disease progression.