Ontology highlight
ABSTRACT:
PROVIDER: PRJNA975456 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24717222.fastq.gz | Fastqsanger.gz | |||
| SRR24717223.fastq.gz | Fastqsanger.gz | |||
| SRR24717224.fastq.gz | Fastqsanger.gz | |||
| SRR24717225.fastq.gz | Fastqsanger.gz | |||
| SRR24717226.fastq.gz | Fastqsanger.gz |
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Project description:Chronic myeloid leukemia (CML) epitomizes successful targeted therapy, with 86% of patients in the chronic phase treated with tyrosine kinase inhibitors (TKIs) attaining remission. However, resistance to TKIs occurs during treatment, and patients with resistance to TKIs progress to the acute phase called Blast Crisis (BC), wherein the survival is restricted to 7-11 months. About 80 % of patients in BC are unresponsive to TKIs. This issue can be addressed by identifying a molecular signature which can predict resistance in CML-CP prior to treatment as well as by delineating the molecular mechanism underlying resistance. Herein, we report genomic analysis of CML patients and imatinib-resistant K562 cell line to achieve the same. Thirteen CML patients (sensitive and resistant to TKIs) and 2 BMT donors (as control) were recruited for the study. DNA was isolated from an enriched CD34+ fraction for each sample as well as from K562 cells made resistant to imatinib which provided a model system for further molecular investigations. DNA was subjected to Cytoscan HD array (Affymatrix) analysis from patient samples and cell lines. Affymetrix CytoScan™ HD array (Applied Biosystems™, Cat# 901835) chip consists of 2.6 M oligonucleotide probes across the genome, including 1953K unique non-polymorphic probes and 750K bi-allelic SNP (single nucleotide polymorphism) probes. Our study identified accumulation of aberrations on chromosomes 1, 3, 7, 16 and 22 as predictive of occurrence of resistance. Further, recurrent amplification in chromosomal region 8q11.2-12.1 was detected in highly resistant K562 cells as well as CML patients. The genes present in this region were analyzed to understand molecular mechanism of imatinib resistance.
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