Prospective Isolation and Characterization of Genetically and Functionally Distinct AML Subclones
Menée in vitro et à l'aide d'une xénogreffe sur un modèle murin, cette étude identifie 50 protéines membranaires plasmatiques permettant, dans la pratique clinique en routine, d'isoler des sous-clones cellulaires distincts de leucémie myéloïde aiguë et d'affiner ainsi le diagnostic
Intra-tumor heterogeneity caused by clonal evolution is a major problem in cancer treatment. To address this problem, we performed label-free quantitative proteomics on primary acute myeloid leukemia (AML) samples. We identified 50 leukemia-enriched plasma membrane proteins enabling the prospective isolation of genetically distinct subclones from individual AML patients. Subclones differed in their regulatory phenotype, drug sensitivity, growth, and engraftment behavior, as determined by RNA sequencing, DNase I hypersensitive site mapping, transcription factor occupancy analysis, in vitro culture, and xenograft transplantation. Finally, we show that these markers can be used to identify and longitudinally track distinct leukemic clones in patients in routine diagnostics. Our study describes a strategy for a major improvement in stratifying cancer diagnosis and treatment.
Cancer Cell , résumé, 2017