Loss of expression of both miR-15/16 loci in CML transition to blast crisis.
Adult
Blast Crisis
/ genetics
Disease Progression
Female
Gene Expression Regulation, Leukemic
Genetic Loci
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
/ genetics
Male
MicroRNAs
/ genetics
Middle Aged
Polycomb Repressive Complex 1
/ genetics
Proto-Oncogene Proteins c-bcl-2
/ genetics
Receptor Tyrosine Kinase-like Orphan Receptors
/ genetics
blast crisis
chronic myeloid leukemia
miR-15/16 cluster
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
16 03 2021
16 03 2021
Historique:
entrez:
10
4
2021
pubmed:
11
4
2021
medline:
10
9
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33836616
pii: 2101566118
doi: 10.1073/pnas.2101566118
pmc: PMC7980455
pii:
doi:
Substances chimiques
BCL2 protein, human
0
BMI1 protein, human
0
MIRN15 microRNA, human
0
MIRN16 microRNA, human
0
MicroRNAs
0
Proto-Oncogene Proteins c-bcl-2
0
Polycomb Repressive Complex 1
EC 2.3.2.27
ROR1 protein, human
EC 2.7.10.1
Receptor Tyrosine Kinase-like Orphan Receptors
EC 2.7.10.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : P30 CA016058
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197706
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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