Differential Regulation of Telomeric Complex by BCR-ABL1 Kinase in Human Cellular Models of Chronic Myeloid Leukemia—From Single Cell Analysis to Next-Generation Sequencing

Genes

卷:11

Anna Deregowska¹  Maciej Wnuk¹  Katarzyna Pruszczyk²  Tomasz Stoklosa³  MarcinM. Machnicki⁴  Monika Pepek⁴ 

[1] Department of Biotechnology, University of Rzeszow, Pigonia 1, 35-310 Rzeszów, Poland;

[2] Department of Immunology, Medical University of Warsaw, Nielubowicza 5, 02-097 Warsaw, Poland;

[3] Department of Tumor Biology and Genetics, Medical University of Warsaw, Pawinskiego 7, 02-106 Warsaw, Poland;

[4] Postgraduate School of Molecular Medicine, Medical University of Warsaw, Trojdena 2a, 02-091 Warsaw, Poland;

关键词: chronic myeloid leukemia;    blast crisis;    BCR-ABL1;    telomere length;    telomerase;    shelterin complex;   

DOI  :  10.3390/genes11101145

来源: DOAJ

【 摘 要 】

Telomeres are specialized nucleoprotein complexes, localized at the physical ends of chromosomes, that contribute to the maintenance of genome stability. One of the features of chronic myeloid leukemia (CML) cells is a reduction in telomere length which may result in increased genomic instability and progression of the disease. Aberrant telomere maintenance in CML is not fully understood and other mechanisms such as the alternative lengthening of telomeres (ALT) are involved. In this work, we employed five BCR-ABL1-positive cell lines, namely K562, KU-812, LAMA-84, MEG-A2, and MOLM-1, commonly used in the laboratories to study the link between mutation, copy number, and expression of telomere maintenance genes with the expression, copy number, and activity of BCR-ABL1. Our results demonstrated that the copy number and expression of BCR-ABL1 are crucial for telomere lengthening. We observed a correlation between BCR-ABL1 expression and telomere length as well as shelterins upregulation. Next-generation sequencing revealed pathogenic variants and copy number alterations in major tumor suppressors, such as TP53 and CDKN2A, but not in telomere-associated genes. Taken together, we showed that BCR-ABL1 kinase expression and activity play a crucial role in the maintenance of telomeres in CML cell lines. Our results may help to validate and properly interpret results obtained by many laboratories employing these in vitro models of CML.

【 授权许可】

Unknown