Acquired miR-142 deficit in leukemic stem cells suffices to drive chronic myeloid leukemia into blast crisis.

Autor: Zhang B; Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research Institute, Duarte, CA, USA. bzhang@coh.org., Zhao D; Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research Institute, Duarte, CA, USA., Chen F; Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research Institute, Duarte, CA, USA., Frankhouser D; Department of Computational and Quantitative Medicine, City of Hope Medical Center and Beckman Research Institute, Duarte, CA, USA., Wang H; Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research Institute, Duarte, CA, USA.; Department of Hematology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China., Pathak KV; Cancer & Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA.; Integrated Mass Spectrometry Shared Resource, City of Hope Comprehensive Cancer Center, Duarte, CA, USA., Dong L; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA, USA., Torres A; Cancer & Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA.; Integrated Mass Spectrometry Shared Resource, City of Hope Comprehensive Cancer Center, Duarte, CA, USA., Garcia-Mansfield K; Cancer & Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA.; Integrated Mass Spectrometry Shared Resource, City of Hope Comprehensive Cancer Center, Duarte, CA, USA., Zhang Y; Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research Institute, Duarte, CA, USA.; Department of Hematology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China., Hoang DH; Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research Institute, Duarte, CA, USA., Chen MH; City of Hope National Medical Center, Integrative Genomics Core, Department of Computational and Quantitative Medicine, Beckman Research Institute, Duarte, CA, USA., Tao S; City of Hope National Medical Center, Integrative Genomics Core, Department of Computational and Quantitative Medicine, Beckman Research Institute, Duarte, CA, USA., Cho H; City of Hope National Medical Center, Integrative Genomics Core, Department of Computational and Quantitative Medicine, Beckman Research Institute, Duarte, CA, USA., Liang Y; DNA/RNA Peptide Shared Resources, Beckman Research Institute, Duarte, CA, USA., Perrotti D; Department of Medicine and Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine Baltimore, Baltimore, MD, USA.; Department of Immunology and Inflammation, Centre of Hematology, Imperial College of London, London, UK., Branciamore S; Department of Computational and Quantitative Medicine, City of Hope Medical Center and Beckman Research Institute, Duarte, CA, USA., Rockne R; Department of Computational and Quantitative Medicine, City of Hope Medical Center and Beckman Research Institute, Duarte, CA, USA., Wu X; City of Hope National Medical Center, Integrative Genomics Core, Department of Computational and Quantitative Medicine, Beckman Research Institute, Duarte, CA, USA., Ghoda L; Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research Institute, Duarte, CA, USA., Li L; Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research Institute, Duarte, CA, USA., Jin J; Department of Hematology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China., Chen J; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA, USA., Yu J; Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA., Caligiuri MA; Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA., Kuo YH; Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research Institute, Duarte, CA, USA., Boldin M; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA, USA., Su R; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA, USA., Swiderski P; DNA/RNA Peptide Shared Resources, Beckman Research Institute, Duarte, CA, USA., Kortylewski M; Department of Immuno-Oncology, Beckman Research Institute, Duarte, CA, USA., Pirrotte P; Cancer & Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA.; Integrated Mass Spectrometry Shared Resource, City of Hope Comprehensive Cancer Center, Duarte, CA, USA., Nguyen LXT; Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research Institute, Duarte, CA, USA. lenguyen@coh.org.; Cancer & Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA. lenguyen@coh.org., Marcucci G; Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research Institute, Duarte, CA, USA. gmarcucci@coh.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Sep 01; Vol. 14 (1), pp. 5325. Date of Electronic Publication: 2023 Sep 01.
DOI: 10.1038/s41467-023-41167-z
Abstrakt: The mechanisms underlying the transformation of chronic myeloid leukemia (CML) from chronic phase (CP) to blast crisis (BC) are not fully elucidated. Here, we show lower levels of miR-142 in CD34 + CD38 - blasts from BC CML patients than in those from CP CML patients, suggesting that miR-142 deficit is implicated in BC evolution. Thus, we create miR-142 knockout CML (i.e., miR-142 -/- BCR-ABL) mice, which develop BC and die sooner than miR-142 wt CML (i.e., miR-142 +/+ BCR-ABL) mice, which instead remain in CP CML. Leukemic stem cells (LSCs) from miR-142 -/- BCR-ABL mice recapitulate the BC phenotype in congenic recipients, supporting LSC transformation by miR-142 deficit. State-transition and mutual information analyses of "bulk" and single cell RNA-seq data, metabolomic profiling and functional metabolic assays identify enhanced fatty acid β-oxidation, oxidative phosphorylation and mitochondrial fusion in LSCs as key steps in miR-142-driven BC evolution. A synthetic CpG-miR-142 mimic oligodeoxynucleotide rescues the BC phenotype in miR-142 -/- BCR-ABL mice and patient-derived xenografts.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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