A longitudinal single-cell atlas of treatment response in pediatric AML
Sander Lambo, Diane L. Trinh, Rhonda E. Ries, Dan Jin, Audi Setiadi, Michelle Ng, Véronique Leblanc, Michael R. Loken, Lisa Eidenschink Brodersen, Fangyan Dai, Laura Pardo, Xiaotu Ma, Suzanne Vercauteren, Soheil Meshinchi, Marco A. Marra
Abstract
Pediatric acute myeloid leukemia (pAML) is characterized by heterogeneous cellular composition, driver alterations and prognosis. Characterization of this heterogeneity and how it affects treatment response remains understudied in pediatric patients. We used single-cell RNA sequencing and single-cell ATAC sequencing to profile 28 patients representing different pAML subtypes at diagnosis, remission and relapse. At diagnosis, cellular composition differed between genetic subgroups. Upon relapse, cellular hierarchies transitioned toward a more primitive state regardless of subtype. Primitive cells in the relapsed tumor were distinct compared to cells at diagnosis, with under-representation of myeloid transcriptional programs and over-representation of other lineage programs. In some patients, this was accompanied by the appearance of a B-lymphoid-like hierarchy. Our data thus reveal the emergence of apparent subtype-specific plasticity upon treatment and inform on potentially targetable processes.