| Autor: |
Christina Zeller, Daniel Richter, Vindi Jurinovic, Ilse A. Valtierra-Gutiérrez, Ashok Kumar Jayavelu, Matthias Mann, Johannes W. Bagnoli, Ines Hellmann, Tobias Herold, Wolfgang Enard, Binje Vick, Irmela Jeremias |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Journal of Hematology & Oncology, Vol 15, Iss 1, Pp 1-6 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1756-8722 |
| DOI: |
10.1186/s13045-022-01232-4 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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