PMID- 37658085
OWN - NLM
STAT- MEDLINE
DCOM- 20230911
LR  - 20240212
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 14
IP  - 1
DP  - 2023 Sep 1
TI  - Acquired miR-142 deficit in leukemic stem cells suffices to drive chronic myeloid 
      leukemia into blast crisis.
PG  - 5325
LID - 10.1038/s41467-023-41167-z [doi]
LID - 5325
AB  - 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 beta-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.
CI  - (c) 2023. Springer Nature Limited.
FAU - Zhang, Bin
AU  - Zhang B
AUID- ORCID: 0000-0003-4703-7524
AD  - 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.
FAU - Zhao, Dandan
AU  - Zhao D
AD  - Department of Hematological Malignancies Translational Science, Gehr Family 
      Center for Leukemia Research, City of Hope Medical Center and Beckman Research 
      Institute, Duarte, CA, USA.
FAU - Chen, Fang
AU  - Chen F
AD  - Department of Hematological Malignancies Translational Science, Gehr Family 
      Center for Leukemia Research, City of Hope Medical Center and Beckman Research 
      Institute, Duarte, CA, USA.
FAU - Frankhouser, David
AU  - Frankhouser D
AUID- ORCID: 0000-0002-8233-5853
AD  - Department of Computational and Quantitative Medicine, City of Hope Medical 
      Center and Beckman Research Institute, Duarte, CA, USA.
FAU - Wang, Huafeng
AU  - Wang H
AD  - Department of Hematological Malignancies Translational Science, Gehr Family 
      Center for Leukemia Research, City of Hope Medical Center and Beckman Research 
      Institute, Duarte, CA, USA.
AD  - Department of Hematology, the First Affiliated Hospital, College of Medicine, 
      Zhejiang University, Hangzhou, Zhejiang, PR China.
FAU - Pathak, Khyatiben V
AU  - Pathak KV
AD  - Cancer & Cell Biology Division, Translational Genomics Research Institute, 
      Phoenix, AZ, USA.
AD  - Integrated Mass Spectrometry Shared Resource, City of Hope Comprehensive Cancer 
      Center, Duarte, CA, USA.
FAU - Dong, Lei
AU  - Dong L
AD  - Department of Systems Biology, Beckman Research Institute of City of Hope, 
      Monrovia, CA, USA.
FAU - Torres, Anakaren
AU  - Torres A
AD  - Cancer & Cell Biology Division, Translational Genomics Research Institute, 
      Phoenix, AZ, USA.
AD  - Integrated Mass Spectrometry Shared Resource, City of Hope Comprehensive Cancer 
      Center, Duarte, CA, USA.
FAU - Garcia-Mansfield, Krystine
AU  - Garcia-Mansfield K
AUID- ORCID: 0000-0002-9089-2254
AD  - Cancer & Cell Biology Division, Translational Genomics Research Institute, 
      Phoenix, AZ, USA.
AD  - Integrated Mass Spectrometry Shared Resource, City of Hope Comprehensive Cancer 
      Center, Duarte, CA, USA.
FAU - Zhang, Yi
AU  - Zhang Y
AD  - Department of Hematological Malignancies Translational Science, Gehr Family 
      Center for Leukemia Research, City of Hope Medical Center and Beckman Research 
      Institute, Duarte, CA, USA.
AD  - Department of Hematology, the First Affiliated Hospital, College of Medicine, 
      Zhejiang University, Hangzhou, Zhejiang, PR China.
FAU - Hoang, Dinh Hoa
AU  - Hoang DH
AD  - Department of Hematological Malignancies Translational Science, Gehr Family 
      Center for Leukemia Research, City of Hope Medical Center and Beckman Research 
      Institute, Duarte, CA, USA.
FAU - Chen, Min-Hsuan
AU  - Chen MH
AD  - City of Hope National Medical Center, Integrative Genomics Core, Department of 
      Computational and Quantitative Medicine, Beckman Research Institute, Duarte, CA, 
      USA.
FAU - Tao, Shu
AU  - Tao S
AUID- ORCID: 0000-0001-5177-6771
AD  - City of Hope National Medical Center, Integrative Genomics Core, Department of 
      Computational and Quantitative Medicine, Beckman Research Institute, Duarte, CA, 
      USA.
FAU - Cho, Hyejin
AU  - Cho H
AUID- ORCID: 0000-0002-9954-8118
AD  - City of Hope National Medical Center, Integrative Genomics Core, Department of 
      Computational and Quantitative Medicine, Beckman Research Institute, Duarte, CA, 
      USA.
FAU - Liang, Yong
AU  - Liang Y
AUID- ORCID: 0000-0002-7225-7062
AD  - DNA/RNA Peptide Shared Resources, Beckman Research Institute, Duarte, CA, USA.
FAU - Perrotti, Danilo
AU  - Perrotti D
AD  - Department of Medicine and Greenebaum Comprehensive Cancer Center, University of 
      Maryland School of Medicine Baltimore, Baltimore, MD, USA.
AD  - Department of Immunology and Inflammation, Centre of Hematology, Imperial College 
      of London, London, UK.
FAU - Branciamore, Sergio
AU  - Branciamore S
AD  - Department of Computational and Quantitative Medicine, City of Hope Medical 
      Center and Beckman Research Institute, Duarte, CA, USA.
FAU - Rockne, Russell
AU  - Rockne R
AUID- ORCID: 0000-0002-1557-159X
AD  - Department of Computational and Quantitative Medicine, City of Hope Medical 
      Center and Beckman Research Institute, Duarte, CA, USA.
FAU - Wu, Xiwei
AU  - Wu X
AD  - City of Hope National Medical Center, Integrative Genomics Core, Department of 
      Computational and Quantitative Medicine, Beckman Research Institute, Duarte, CA, 
      USA.
FAU - Ghoda, Lucy
AU  - Ghoda L
AD  - Department of Hematological Malignancies Translational Science, Gehr Family 
      Center for Leukemia Research, City of Hope Medical Center and Beckman Research 
      Institute, Duarte, CA, USA.
FAU - Li, Ling
AU  - Li L
AUID- ORCID: 0000-0001-7568-939X
AD  - Department of Hematological Malignancies Translational Science, Gehr Family 
      Center for Leukemia Research, City of Hope Medical Center and Beckman Research 
      Institute, Duarte, CA, USA.
FAU - Jin, Jie
AU  - Jin J
AD  - Department of Hematology, the First Affiliated Hospital, College of Medicine, 
      Zhejiang University, Hangzhou, Zhejiang, PR China.
FAU - Chen, Jianjun
AU  - Chen J
AUID- ORCID: 0000-0003-3749-2902
AD  - Department of Systems Biology, Beckman Research Institute of City of Hope, 
      Monrovia, CA, USA.
FAU - Yu, Jianhua
AU  - Yu J
AUID- ORCID: 0000-0002-0326-3223
AD  - Department of Hematology & Hematopoietic Cell Transplantation, City of Hope 
      National Medical Center, Duarte, CA, USA.
FAU - Caligiuri, Michael A
AU  - Caligiuri MA
AUID- ORCID: 0000-0002-4095-3020
AD  - Department of Hematology & Hematopoietic Cell Transplantation, City of Hope 
      National Medical Center, Duarte, CA, USA.
FAU - Kuo, Ya-Huei
AU  - Kuo YH
AUID- ORCID: 0000-0003-2595-0419
AD  - Department of Hematological Malignancies Translational Science, Gehr Family 
      Center for Leukemia Research, City of Hope Medical Center and Beckman Research 
      Institute, Duarte, CA, USA.
FAU - Boldin, Mark
AU  - Boldin M
AD  - Department of Systems Biology, Beckman Research Institute of City of Hope, 
      Monrovia, CA, USA.
FAU - Su, Rui
AU  - Su R
AUID- ORCID: 0000-0002-4807-6229
AD  - Department of Systems Biology, Beckman Research Institute of City of Hope, 
      Monrovia, CA, USA.
FAU - Swiderski, Piotr
AU  - Swiderski P
AD  - DNA/RNA Peptide Shared Resources, Beckman Research Institute, Duarte, CA, USA.
FAU - Kortylewski, Marcin
AU  - Kortylewski M
AUID- ORCID: 0000-0002-6003-1816
AD  - Department of Immuno-Oncology, Beckman Research Institute, Duarte, CA, USA.
FAU - Pirrotte, Patrick
AU  - Pirrotte P
AUID- ORCID: 0000-0003-1360-6039
AD  - Cancer & Cell Biology Division, Translational Genomics Research Institute, 
      Phoenix, AZ, USA.
AD  - Integrated Mass Spectrometry Shared Resource, City of Hope Comprehensive Cancer 
      Center, Duarte, CA, USA.
FAU - Nguyen, Le Xuan Truong
AU  - Nguyen LXT
AD  - 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.
AD  - Cancer & Cell Biology Division, Translational Genomics Research Institute, 
      Phoenix, AZ, USA. lenguyen@coh.org.
FAU - Marcucci, Guido
AU  - Marcucci G
AUID- ORCID: 0000-0002-3983-5908
AD  - 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.
LA  - eng
GR  - P30 CA033572/CA/NCI NIH HHS/United States
GR  - R01 CA205247/CA/NCI NIH HHS/United States
GR  - R01 CA248475/CA/NCI NIH HHS/United States
GR  - R01 CA258981/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20230901
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (MicroRNAs)
RN  - 0 (MIRN142 microRNA, human)
RN  - 0 (Mirn142 microRNA, mouse)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - Blast Crisis
MH  - *Leukemia, Myelogenous, Chronic, BCR-ABL Positive
MH  - *Leukemia, Myeloid
MH  - *Leukemia, Myeloid, Chronic-Phase
MH  - *MicroRNAs
MH  - Stem Cells
PMC - PMC10474062
COIS- The authors declare no competing interests.
EDAT- 2023/09/02 05:42
MHDA- 2023/09/07 06:42
PMCR- 2023/09/01
CRDT- 2023/09/01 23:19
PHST- 2022/11/07 00:00 [received]
PHST- 2023/08/23 00:00 [accepted]
PHST- 2023/09/07 06:42 [medline]
PHST- 2023/09/02 05:42 [pubmed]
PHST- 2023/09/01 23:19 [entrez]
PHST- 2023/09/01 00:00 [pmc-release]
AID - 10.1038/s41467-023-41167-z [pii]
AID - 41167 [pii]
AID - 10.1038/s41467-023-41167-z [doi]
PST - epublish
SO  - Nat Commun. 2023 Sep 1;14(1):5325. doi: 10.1038/s41467-023-41167-z.