The interplay between telomeric complex members and BCR::ABL1 oncogenic tyrosine kinase in the maintenance of telomere length in chronic myeloid leukemia.
J Cancer Res Clin Oncol
; 149(10): 7103-7112, 2023 Aug.
Article
en En
| MEDLINE
| ID: mdl-36871092
ABSTRACT
PURPOSE:
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by recurrent genetic aberration in leukemic stem cells, namely Philadelphia chromosome caused by reciprocal translocation t(9;22)(q34;q11). In our study, we analyzed the telomeric complex expression and function in the molecular pathogenesis of CML.METHODS:
We employed CD34+ primary leukemic cells, comprising both leukemic stem and progenitor cell populations, isolated from peripheral blood or bone marrow of CML patients in chronic and blastic phase to analyze the telomere length and telomeric-associated proteins.RESULTS:
The reduction in telomere length during disease progression was correlated with increased expression of BCRABL1 transcript and the dynamic changes were neither associated with the enzymatic activity of telomerase nor with gene copy number and expression of telomerase subunits. Increased expression of BCRABL1 was positively correlated with expression of TRF2, RAP1, TPP1, DKC1, TNKS1, and TNKS2 genes.CONCLUSIONS:
The dynamics of telomere length changes in CD34+ CML cells is dependent on the expression level of BCRABL, which promotes the expression of certain shelterins including RAP1 and TRF2, as well as TNKS, and TNKS2, and results in telomere shortening regardless of telomerase activity. Our results may allow better understanding of the mechanisms responsible for the genomic instability of leukemic cells and CML progression.Palabras clave
Texto completo:
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Banco de datos:
MEDLINE
Asunto principal:
Leucemia Mielógena Crónica BCR-ABL Positiva
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Telomerasa
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Tanquirasas
Límite:
Humans
Idioma:
En
Año:
2023
Tipo del documento:
Article