Targeting glucocorticoid-induced CD20 activation in preclinical models of B-ALL

However, relapse occurs in 15-20% of patients due to minimal residual disease (MRD), characterized by the presence of persisting and resistant leukemic cells, and associated with a poor clinical outcome. Despite its prognostic relevance, the molecular features driving MRD are poorly characterized.

In this study, we developed patient-derived xenograft (PDX) models from matched diagnosis and relapse B‑ALL samples combined to chemotherapy to mimic MRD in vivo. Drug-tolerant leukemic cells were profiled using single-cell RNA sequencing and we identified a transcriptionally distinct MRD-like population enriched for cell-quiescence, inflammatory stress, and B‑cell receptor pathway signatures. Strikingly, the B-lymphocyte surface antigen CD20, encoding by MS4A1 gene, emerged as a consistent up-regulated marker in MRD cells from PDXs and patients with diverse oncogenic subtypes.