A longitudinal single-cell atlas of treatment response in pediatric AML (scRNA-Seq)

Pediatric acute myeloid leukemia (pAML) is a disease characterized by heterogeneous cellular composition, driver alterations and prognosis. Characterization of this heterogeneity and how it affects treatment response remains relatively understudied in pediatric patients. We therefore used single-cell RNA sequencing and single-cell ATAC sequencing to profile 684,031 diagnosis, remission and relapse cells from 28 patients representing different pAML subtypes. Analysis revealed that at diagnosis, cellular compositions differed between distinct subgroups. Upon relapse, cellular hierarchies transitioned towards a more primitive state regardless of subtype. These primitive cells were distinct compared to cells at diagnosis, having underrepresentation of transcriptional programs involved in myeloid differentiation while programs commonly found in other lineages were overrepresented. In a subset of patients, this appeared to accompany the appearance of a B-lymphoid-like hierarchy. Together, our data reveal the emergence of apparent subtype-specific plasticity upon treatment and inform on potential novel therapeutic angles to target these cell populations. Single cell RNA sequencing from 28 matched patient tumors enrolled in the study. Biopsies were taken from bone marrow or peripheral blood at diagnosis, remission and relapse and Ficoll-enriched. ----------------------------------- Authors state: Raw data have not been uploaded as it concerns sequencing data from patients. These data are in the process of being uploaded to the protected environment of EGA under accession number EGAS00001007323.