Acute myeloid leukemia (AML) patients suffer dismal prognosis upon treatment resistance. To study functional heterogeneity of resistance, we generated serially transplantable patient-derived xenograft (PDX) models from one patient with AML and twelve clones thereof, each derived from a single stem cell, as proven by genetic barcoding. Transcriptome and exome sequencing segregated clones according to their origin from relapse one or two. Undetectable for sequencing, multiplex fluorochrome-guided competitive in vivo treatment trials identified a subset of relapse two clones as uniquely resistant to cytarabine treatment. Transcriptional and proteomic profiles obtained from resistant PDX clones and refractory AML patients defined a 16-gene score that was predictive of clinical outcome in a large independent patient cohort. Thus, we identified novel genes related to cytarabine resistance and provide proof of concept that intra-tumor heterogeneity reflects inter-tumor heterogeneity in AML.
CITATION STYLE
Zeller, C., Richter, D., Jurinovic, V., Valtierra-Gutiérrez, I. A., Jayavelu, A. K., Mann, M., … Jeremias, I. (2022, December 1). Adverse stem cell clones within a single patient’s tumor predict clinical outcome in AML patients. Journal of Hematology and Oncology. BioMed Central Ltd. https://doi.org/10.1186/s13045-022-01232-4
Mendeley helps you to discover research relevant for your work.