miR-126 identifies a quiescent and chemo-resistant human B-ALL cell subset that correlates with minimal residual disease [scRNAseq]

Complete elimination of B-cell acute lymphoblastic leukemia (B-ALL) by a risk-adapted primary treatment approach remains a clinical key objective, which fails in up to a third of patients. We hypothesized that microRNA-126, a core regulator of hematopoietic and leukemic stem cells, may resolve intra-tumor heterogeneity in B-ALL and uncover therapy-resistant subpopulations. By means of a miR-126-high signature (obtained by transducing primary human-B-all cells with a miR-126 reporter vector) and single cell RNA sequencing we identified a miR-126 derived intra tumoral heterogeneity in unmanipulated primary human B-ALL blasts Overall design: To unravel the role of miR-126 in leukemia heterogeneity in unmanipulated blasts we performed an extensive transcriptomic analysis on 5 primary B-ALL (4 adults and 1 pediatric) by single cell RNAsequencing. The obtained data were interrogated with a miR-126 high signature and we were able to detect a miR-126 intra tumoral heterogeneity even on this un-manipulated primary samples.