| First Author | Zhang B | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 5325 |
| PubMed ID | 37658085 | Mgi Jnum | J:340297 |
| Mgi Id | MGI:7527887 | Doi | 10.1038/s41467-023-41167-z |
| Citation | Zhang B, et al. (2023) Acquired miR-142 deficit in leukemic stem cells suffices to drive chronic myeloid leukemia into blast crisis. Nat Commun 14(1):5325 |
| abstractText | 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. |
