Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA312395 | ENA |
REPOSITORIES: ENA
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Project description:Using a microarray-based miRNA profiling, we found in a model of chronic myeloid leukemia (CML) that the activity of the oncoprotein BCR-ABL1 regulates the expression of miR-21, a "onco-microRNA" known to be overexpressed in numerous cancers. This relies on the phosphorylation status of STAT5, a transcription factor known to be activated by the kinase activity of BCR-ABL1. Mir-21 regulates the expression of PDCD4 (programmed cell death protein 4), a tumor suppressor identified here through a proteomics approach The microRNA repertoire of K562 cells having been either not treated (n=3) or treated (n=3) with the tyrosine kinase inhibitor Imatinib (1microM, 24h) was studied using Agilent microRNA V2 microarrays
2016-09-01 | E-GEOD-78037 | biostudies-arrayexpress
Project description:Chronic myelogenous leukemia (CML) is a malignant stem cell disease characterized by a reciprocal translocation between chromosome 9 and 22. The selective bcr-abl tyrosine-kinase inhibitor Imatinib has become the therapy of choice for patients with newly diagnosed CML including those previously considered candidates for allogeneic haematopoietic stem cell transplantation. The tyrosine-kinase inhibitor Nilotinib is a derivate of Imatinib with higher potency. To examine the molecular and functional effects of Nilotinib and Imatinib in chronic myelogenous leukemia, we performed gene expression and functional analyses in K562 cells following treatment with the two tyrosine kinase inhibitors. Experiment Overall Design: Affymetrix U133A 2.0 microarrays were used to examine the gene expression profile of K562 cells after in vitro treatment with Imatinib (0.5 µM) or Nilotinib (0.05 µM) for 24 hours. Gene expression data of the treated cells were compared with data of untreated cells.
2010-01-19 | E-GEOD-19567 | biostudies-arrayexpress
Project description:K562 cell line mock treated or for 24 hours with one micromolar imatinib. Keywords: other
2004-11-03 | GSE1922 | GEO
Project description:Chronic myeloid leukemia is a malignant hematopoietic disorder distinguished by a presence of BCR-ABL fused oncogene with constitutive kinase activity. Although targeted therapy by tyrosine kinase inhibitors (TKI) markedly improved patient´s survival and quality of life, development of drug resistance remains a critical issue for a subset of patients. The most common mechanism of TKI resistance in CML patients is a mutation in BCR-ABL gene which makes oncogenic Bcr-Abl protein insensitive to TKI therapy. Mutation independent mechanisms of TKI resistance are less elucidated, but exosomes, extracellular vesicles excreted from normal and tumor cells were recently linked with cancer progression and drug resistance. We used an imatinib-sensitive CML cell line K562 and derived an imatinib-resistant subline K562IR by prolonged cultivation of cells in presence of imatinib. We demonstrated that exosomes isolated from K562IR cells are internalized by K562 cells and increase their survival in presence of 2µM imatinib. To characterize the exosomal cargo and to identify resistance-associated marker proteins, we performed a deep proteomic analysis of exosomes from both cell sublines using label free quantification (LFQ). In total, we identified over 3000 exosomal proteins including 31 proteins differentially abundant in exosomes derived from K562IR cells. Among the differential proteins were three massively upregulated membrane proteins in K562IR exosomes with surface localization: IFITM3, CD146, CD36. We verified the massive upregulation of the three proteins in K562IR exosomes and also in K562IR cells. Using flow cytometry, we further demonstrated potential of CD146 as cell surface marker associated with imatinib resistance in K562 cells.
2024-10-24 | PXD019283 | Pride
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
Project description:The Bmi1 Polycomb protein is involved in the epigenetic repressive control of self renewal and survival of cancer initiating cells. In Chronic Myeloid Leukemia (CML), bmi1 expression increases gradually as the disease progresses from a chronic latent phase to a deadly blast crisis. We developped an inducible shRNA system to silence Bmi1 in the human K562 chronic myeloid leukemia (CML) cell line in order to identify new Bmi1-target genes. Gene profiling was performed on inducible shBmi1-K562 cells incubated without (P3-K562+shBMI1) or with doxycycline for 96h (P4-K562+shBMI1+doxycycline) using HG-U133 Plus2 Affymetrix Arrays.
2015-05-12 | E-GEOD-54262 | biostudies-arrayexpress
Project description:K562 cell line mock treated or for 24 hours with one micromolar imatinib.
2008-06-12 | E-GEOD-1922 | biostudies-arrayexpress
Project description:In order to indetify new target genes of miR-92a-1-5p in chronic myeloid leukemia, K562 cells carrying the BCR::ABL1 fusion gene were transiently transfected with miR-92a mimic or scramble and treated with imatinib. RNA was sequenced to identify genes expressed under imatinib treatment and downregulated after miR-92a-1-5p overexpression.
2024-10-11 | GSE278906 | GEO
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: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.
2024-01-01 | E-MTAB-11899 | biostudies-arrayexpress