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

Standard

Adverse stem cell clones within a single patient's tumor predict clinical outcome in AML patients. / Zeller, Christina; Richter, Daniel; Jurinovic, Vindi; Valtierra-Gutiérrez, Ilse A; Jayavelu, Ashok Kumar; Mann, Matthias; Bagnoli, Johannes W; Hellmann, Ines; Herold, Tobias; Enard, Wolfgang; Vick, Binje; Jeremias, Irmela.

In: Journal of Hematology & Oncology, Vol. 15, No. 1, 12.03.2022, p. 25.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Zeller, C, Richter, D, Jurinovic, V, Valtierra-Gutiérrez, IA, Jayavelu, AK, Mann, M, Bagnoli, JW, Hellmann, I, Herold, T, Enard, W, Vick, B & Jeremias, I 2022, 'Adverse stem cell clones within a single patient's tumor predict clinical outcome in AML patients', Journal of Hematology & Oncology, vol. 15, no. 1, pp. 25. https://doi.org/10.1186/s13045-022-01232-4

APA

Zeller, C., Richter, D., Jurinovic, V., Valtierra-Gutiérrez, I. A., Jayavelu, A. K., Mann, M., Bagnoli, J. W., Hellmann, I., Herold, T., Enard, W., Vick, B., & Jeremias, I. (2022). Adverse stem cell clones within a single patient's tumor predict clinical outcome in AML patients. Journal of Hematology & Oncology, 15(1), 25. https://doi.org/10.1186/s13045-022-01232-4

Vancouver

Zeller C, Richter D, Jurinovic V, Valtierra-Gutiérrez IA, Jayavelu AK, Mann M et al. Adverse stem cell clones within a single patient's tumor predict clinical outcome in AML patients. Journal of Hematology & Oncology. 2022 Mar 12;15(1):25. https://doi.org/10.1186/s13045-022-01232-4

Author

Zeller, Christina ; Richter, Daniel ; Jurinovic, Vindi ; Valtierra-Gutiérrez, Ilse A ; Jayavelu, Ashok Kumar ; Mann, Matthias ; Bagnoli, Johannes W ; Hellmann, Ines ; Herold, Tobias ; Enard, Wolfgang ; Vick, Binje ; Jeremias, Irmela. / Adverse stem cell clones within a single patient's tumor predict clinical outcome in AML patients. In: Journal of Hematology & Oncology. 2022 ; Vol. 15, No. 1. pp. 25.

Bibtex

@article{ff93e41bc26a4136bd178bb7db966981,
title = "Adverse stem cell clones within a single patient's tumor predict clinical outcome in AML patients",
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.",
keywords = "Clone Cells, Cytarabine/therapeutic use, Drug Resistance, Neoplasm/genetics, Humans, Leukemia, Myeloid, Acute/drug therapy, Proteomics, Recurrence, Stem Cells/pathology",
author = "Christina Zeller and Daniel Richter and Vindi Jurinovic and Valtierra-Guti{\'e}rrez, {Ilse A} and Jayavelu, {Ashok Kumar} and Matthias Mann and Bagnoli, {Johannes W} and Ines Hellmann and Tobias Herold and Wolfgang Enard and Binje Vick and Irmela Jeremias",
note = "{\textcopyright} 2022. The Author(s).",
year = "2022",
month = mar,
day = "12",
doi = "10.1186/s13045-022-01232-4",
language = "English",
volume = "15",
pages = "25",
journal = "Journal of Hematology & Oncology",
issn = "1756-8722",
publisher = "BioMed Central",
number = "1",

}

RIS

TY - JOUR

T1 - Adverse stem cell clones within a single patient's tumor predict clinical outcome in AML patients

AU - Zeller, Christina

AU - Richter, Daniel

AU - Jurinovic, Vindi

AU - Valtierra-Gutiérrez, Ilse A

AU - Jayavelu, Ashok Kumar

AU - Mann, Matthias

AU - Bagnoli, Johannes W

AU - Hellmann, Ines

AU - Herold, Tobias

AU - Enard, Wolfgang

AU - Vick, Binje

AU - Jeremias, Irmela

N1 - © 2022. The Author(s).

PY - 2022/3/12

Y1 - 2022/3/12

N2 - 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.

AB - 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.

KW - Clone Cells

KW - Cytarabine/therapeutic use

KW - Drug Resistance, Neoplasm/genetics

KW - Humans

KW - Leukemia, Myeloid, Acute/drug therapy

KW - Proteomics

KW - Recurrence

KW - Stem Cells/pathology

U2 - 10.1186/s13045-022-01232-4

DO - 10.1186/s13045-022-01232-4

M3 - Journal article

C2 - 35279202

VL - 15

SP - 25

JO - Journal of Hematology & Oncology

JF - Journal of Hematology & Oncology

SN - 1756-8722

IS - 1

ER -

ID: 303113164