Dasatinib Resistant K562 cell lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE239677 | GEO | 2023/08/08
REPOSITORIES: GEO
Similar Datasets
Project description:Total RNA from 1e7 K562 cells either mock-treated with DMSO or treated with 100nM dasatinib in two biological repeats for 3 hours
2009-04-02 | E-MEXP-1561 | biostudies-arrayexpress
Project description:Purpose: Several ALL subtypes have been described depending on their karyotype, cell type, immunophenotype and gene-expression profile. Recently, a novel ALL subtype has been described and is characterized by expression of the pre-B cell receptor (pre-BCR). Interestingly, half of the cases is associated with the chromosomal translocation t(1:19), coding for the chimeric fusion protein E2A-PBX1, which is present in about 5% of pediatric and adult ALL. Using preclinical models, we and other groups have shown very promising preclinical activity of dasatinib in pre-BCR+ ALL and early clinical evidence supports our observations. To study mechanism of acquired dasatinib resistance, we generated dasatinib-resistant pre-BCR+/E2A-PBX1+ cell lines through multiple passages in the presence of increasing drug concentrations. Whole transcriptome analysis of dasatinib-sensitive and resistant ALL cells were performed to detect systematically differentially expressed genes and enriched pathways involved in dasatinib resistance.
2018-09-18 | GSE97352 | GEO
Project description:Acquired drug resistance and tumour relapse impacts the majority of patients being treated with tyrosine kinase inhibitors (TKIs) and remains a key challenge in modern anti-cancer therapy. The lack of clinically effective therapeutic strategies to overcome drug resistance represents a significant unmet need. Understanding the signalling pathways that drive drug resistance will facilitate the development of new salvage therapies to effectively treat patients with secondary TKI resistance. In this study, we utilise quantitative mass spectrometry to characterise the global phosphoproteomic alterations that accompany the acquisition of resistance to two FDA-approved multi-target TKIs, pazopanib and dasatinib, in the A204 rhabdoid tumour cell line. Our analysis finds that only a limited fraction of the quantified phosphoproteome (<10%) is altered upon the acquisition of drug resistance with pazopanib resistant cells displaying elevated phosphorylation levels in cytoskeletal regulatory pathways and dasatinib resistant cells showing an upregulation of components of the insulin receptor/IGF1-R signalling pathway. Drug response profiling with a targeted panel of small molecule inhibitors rediscovers several previously reported vulnerabilities associated with pazopanib and dasatinib resistance and identifies a new dependency to the second generation HSP90 inhibitor NVP-AUY-922. This study provides a useful resource detailing the candidate signalling determinants of acquired TKI resistance; and reveals a therapeutic approach of inhibiting HSP90 function as a means of salvage therapy to overcome pazopanib and dasatinib resistance.
2017-08-30 | PXD005536 | Pride
Project description:The aim of the analysis is to study the relationship between tyrosine kinase inhibitor (TKI) resistance mechanism and phenotypic plasticity in the TKI-resistant and parental chronic myeloid leukemia K562 cell lines, in the presence and absence of imatinib. Results provide insight into the molecular mechanisms underlying the acquisition of cancer cell plasticity.
2020-04-14 | GSE120932 | GEO
Project description:Long-term treatment of Kasumi-1 cells at clinically attained doses of dasatinib led to decreased drug-sensitivity by means of IC50 values (relative to treatment-naive cells). Changes were paralled by profound alterations in c-KIT expression and cell signaling signatures. Upon brief discontinuation of dasatinib treatment, these alterations reversed and drug sensitivity was restored. We used gene expression profiling to examine reversal of dasatinib-resistance at the molecular/expression level. Kasumi-1 cells were either treated with dasatinib for 12 weeks (R48) or left untreated (K). Subsequently, dasatinib was withdrawn from R48 cells for 1 week (PR48). RNA was extracted from R48 and K cells and hybridized on Affymetrix microarrays after 12 weeks and PR48 after a total time span of 13 weeks.
2013-11-27 | E-GEOD-39073 | biostudies-arrayexpress
Project description:Long-term treatment of Kasumi-1 cells at clinically attained doses of dasatinib led to decreased drug-sensitivity by means of IC50 values (relative to treatment-naive cells). Changes were paralled by profound alterations in c-KIT expression and cell signaling signatures. Upon brief discontinuation of dasatinib treatment, these alterations reversed and drug sensitivity was restored. We used gene expression profiling to examine reversal of dasatinib-resistance at the molecular/expression level.
2013-11-27 | GSE39073 | GEO
Project description:Gene profiles from three dasatinib-resistant and three dasatinib-sensitive pancreatic cancer cell lines were compared by microarray analysis.
2015-02-24 | GSE59357 | GEO
Project description:A summary of the work associated to these microarrays is the following: The need for an integrated view of all data obtained from high-throughput technologies gave rise to network analyses. These are especially useful to rationalize phenomena in terms of how external perturbations propagate through the expression of genes. To address this issue in the case of drug resistance, we constructed Biological Association Networks of genes differentially expressed in cell lines resistant to methotrexate (MTX). Seven cell lines representative of different types of cancer including colon cancer (HT29 and Caco2), breast cancer (MCF7 and MDA-MB-468), pancreatic cancer (MIA PaCa-2), erythroblastic leukemia (K562) and osteosarcoma (Saos-2), were used. The differential expression pattern between sensitive and MTX-resistant cells was determined by microarrays covering the whole human genome and analyzed with the GeneSpring GX software package, v.7.3.1. Genes deregulated in common in the two colon cancer cell lines studied, were subject of Biological Association Networks construction. Dikkopf homolog-1 (DKK1) was a clear node of this network, and functional validations of this target using a siRNA showed a chemosensitization toward MTX. Members of the UDP-glucuronosyltransferase 1A (UGT1A) family formed a network of differentially expressed genes in the two breast cancer cell lines studied. siRNA treatment against UGT1A showed also an increase in MTX sensitivity. Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) was a gene overexpressed in common among the pancreatic cancer, leukemia and osteosarcoma cell lines, and siRNA treatment against EEF1A1 produced a chemosensitization toward MTX. Biological Association Networks identified DKK1, UGT1As and EEF1A1 as important gene nodes in MTX-resistance. Treatments using iRNA technology against these three genes show chemosensitization toward MTX. Two cell lines are compared, which are K562 erythroblastic leukemia cells sensitive to methotrexate and K562 cells resistant to 10e-5M methotrexate. Six samples are provided which correspond to triplicates of each cell line. The samples provided were analyzed using the specific software GeneSpring GX.
2009-09-08 | E-GEOD-16085 | biostudies-arrayexpress
Project description:Gene profiles from three dasatinib-resistant and three dasatinib-sensitive pancreatic cancer cell lines were compared by microarray analysis. RNA from three dasatinib-resistant (MiaPaCa2, Panc1, SU8686) and three dasatinib-sensitive (Panc0504, Panc0403, Panc1005) pancreatic cancer cell lines were extracted. Biological triplicates were employed for each cell line. Complementary DNA microarray analysis was performed using Illumina Human HT-12 v4 BeadChip (Illumina, San Diego, CA) at the National University of Singapore Core Facility following the manufacturer’s instructions.
2015-02-24 | E-GEOD-59357 | biostudies-arrayexpress
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. WGS was performed on imatinib-sensitive and -resistant K562 cells. Library preparation was done by 30x WGS KAPA PCR-Free v2.1 kit, and Illumina HiSeq X sequencer was used for 2 x 150 bp paired-end sequencing. 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.
2024-01-01 | E-MTAB-11896 | biostudies-arrayexpress