Loss of expression of both miR-15/16 loci in CML transition to blast crisis.
Francesca LovatPierluigi GaspariniGiovanni NigitaKarilyn T M LarkinJohn C ByrdMark D MindenMichael AndreeffBing Z CarterCarlo M CrocePublished in: Proceedings of the National Academy of Sciences of the United States of America (2021)
Despite advances that have improved the treatment of chronic myeloid leukemia (CML) patients in chronic phase, the mechanisms of the transition from chronic phase CML to blast crisis (BC) are not fully understood. Considering the key role of miR-15/16 loci in the pathogenesis of myeloid and lymphocytic leukemia, here we aimed to correlate the expression of miR-15a/16 and miR-15b/16 to progression of CML from chronic phase to BC. We analyzed the expression of the two miR-15/16 clusters in 17 CML patients in chronic phase and 22 patients in BC and in 11 paired chronic phase and BC CML patients. BC CMLs show a significant reduction of the expression of miR-15a/-15b/16 compared to CMLs in chronic phase. Moreover, BC CMLs showed an overexpression of miR-15/16 direct targets such as Bmi-1, ROR1, and Bcl-2 compared to CMLs in chronic phase. This study highlights the loss of both miR-15/16 clusters as a potential oncogenic driver in the transition from chronic phase to BC in CML patients.
Keyphrases
- end stage renal disease
- cell proliferation
- ejection fraction
- long non coding rna
- newly diagnosed
- chronic kidney disease
- chronic myeloid leukemia
- public health
- long noncoding rna
- bone marrow
- gene expression
- dna methylation
- dendritic cells
- risk assessment
- acute myeloid leukemia
- patient reported outcomes
- genome wide
- weight gain
- combination therapy
- human health
- genome wide association study
- smoking cessation