Adverse stem cell clones within a single patient's tumor predict clinical outcome in AML patients
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Journal of Hematology & Oncology |
Volume | 15 |
Issue number | 1 |
Pages (from-to) | 25 |
ISSN | 1756-8722 |
DOIs | |
Publication status | Published - 12 Mar 2022 |
Externally published | Yes |
Bibliographical note
© 2022. The Author(s).
- Clone Cells, Cytarabine/therapeutic use, Drug Resistance, Neoplasm/genetics, Humans, Leukemia, Myeloid, Acute/drug therapy, Proteomics, Recurrence, Stem Cells/pathology
Research areas
ID: 303113164