ArticleJournal of hematology & oncology2022
Adverse stem cell clones within a single patient's tumor predict clinical outcome in AML patients.
Article in Journal of hematology & oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- A platform of serially transplantable AML PDX models covering subgroups for which no cell lines exist.HemaSphere · 2026Article
- Increasing TET Expression and 5-Hydroxymethylcytosine Formation by a Carbocyclic 5-Aza-2'-deoxy-cytidine Antimetabolite.Angewandte Chemie (International ed. in English) · 2026Article
- Enhancer Hijacking Discovery in Acute Myeloid Leukemia by Pyjacker Identifies MNX1 Activation via Deletion 7q.Blood cancer discovery · 2025Article
- Defining 2 biologically and clinically distinct groups in acute leukemia with a mixed phenotype.Blood · 2025Article
- Review
- Investigating resistance to 5-Azacytidine and Venetoclax in PDX models of MDS/AML.Frontiers in oncology · 2024Article
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Authors and funding
12 authors.
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Abstract
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.
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