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Journal of Cancer Research and Clinical Oncology

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Open Access 05-03-2023 | Chronic Myeloid Leukemia | Research

The interplay between telomeric complex members and BCR::ABL1 oncogenic tyrosine kinase in the maintenance of telomere length in chronic myeloid leukemia

Authors: Anna Deręgowska, Monika Pępek, Iwona Solarska, Marcin M. Machnicki, Katarzyna Pruszczyk, Marek Dudziński, Joanna Niesiobędzka-Krężel, Ilona Seferyńska, Waldemar Sawicki, Maciej Wnuk, Tomasz Stokłosa

Published in: Journal of Cancer Research and Clinical Oncology | Issue 10/2023

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 BCR::ABL1 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 BCR::ABL1 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 BCR::ABL, 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.

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Title: The interplay between telomeric complex members and BCR::ABL1 oncogenic tyrosine kinase in the maintenance of telomere length in chronic myeloid leukemia
Authors: Anna Deręgowska
Monika Pępek
Iwona Solarska
Marcin M. Machnicki
Katarzyna Pruszczyk
Marek Dudziński
Joanna Niesiobędzka-Krężel
Ilona Seferyńska
Waldemar Sawicki
Maciej Wnuk
Tomasz Stokłosa
Publication date: 05-03-2023
Publisher: Springer Berlin Heidelberg
Keyword: Chronic Myeloid Leukemia
Published in: Journal of Cancer Research and Clinical Oncology / Issue 10/2023
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-023-04662-w

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