Expression data from iPS cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE37982 | GEO | 2012/05/16
SECONDARY ACCESSION(S): PRJNA167026
REPOSITORIES: GEO
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Project description:We generated iPSCs from imatinib-sensitive chronic myelogenous leukemia (CML) patient samples. We used microarrays tc ompare the gene expression pattern among CML-iPSCs and normal cord blood (CB) iPSCs. Two CML derived iPS cells and one CB derived iPS cells were selected for RNA extraction and hybridization on Affymetrix microarrays.
2012-05-15 | E-GEOD-37982 | 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.
2009-12-19 | GSE19567 | GEO
Project description:This is a class prediction experiment, where the class is the response status to imatinib (also called Gleevec), a drug used to treat patients with chronic myelogenous leukemia (CML). There are two data sets, a training set (from Leipzig, 8 Responders and 5 Non-Responders) and a validation set (from Mannheim, 8 Responders and 7 Non-Responders). The objective is to identify differentially regulated genes between CML patients who respond and those who do not respond to imatinib and confirm the results in the validation data set. The samples from blood or bone marrow of CML patients were hybridized to Affymetrix HG-U95Av2 chip and RMA was used to generate the normalized signal values. Keywords = chronic myelogenous leukemia Keywords = imatinib Keywords = cytogenetic responses Keywords = Gleevec Keywords = Affymetrix Keywords: other
2005-04-18 | GSE2535 | GEO
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:BACKGROUND: BCR-ABL1+ chronic myeloid leukemia (CML) is characterized by abnormal production of leukemic stem (LSC) and progenitor cells and their spread from the bone marrow into the blood resulting in extramedullary myeloproliferation. So far, little is known about specific markers and functions of LSC in CML. METHODS: We examined the phenotype and function of CD34+/CD38─/Lin─ CML LSC by a multi-parameter screen approach employing antibody-phenotyping, mRNA expression profiling, and functional studies, including LSC repopulation experiments in irradiated NOD-SCID-IL-2Rgamma-/- (NSG) mice, followed by marker-validation using diverse control-cohorts and follow-up samples of CML patients treated with imatinib. RESULTS: Of all LSC markers examined, dipeptidylpeptidase IV (DPPIV=CD26) was identified as specific and functionally relevant surface marker-enzyme on CD34+/CD38─ CML LSC. CD26 was not detected on normal CD34+/CD38─ stem cells or LSC in other hematopoietic malignancies. The percentage of CD26+ CML LSC decreased to undetectable levels during successful treatment with imatinib in all patients (p<0.001). Whereas the sorted CD26─ stem cells obtained from CML patients engrafted irradiated NSG mice with multilineage BCR-ABL1-negative hematopoiesis, CD26+ LSC engrafted NSG mice with BCR-ABL1+ cells. Functionally, CD26 was identified as target-enzyme disrupting the SDF-1alpha-CXCR4-axis by cleaving SDF-1alpha a chemotaxin for CXCR4+ stem cells. Whereas CD26 was found to inhibit SDF-1alpha-induced migration, CD26-targeting gliptins reverted this effect and blocked the mobilization of CML LSC in a stroma co-culture assay. CONCLUSIONS: CD26 is a robust biomarker of LSC and a useful tool for their quantification and isolation in patients with BCR/ABL1+ CML. Moreover, CD26 expression may explain the extramedullary spread of LSC in CML. To define specific mRNA expression patterns and to identify specific LSC markers in CML LSC, gene array analyses were performed. RNA was isolated from sorted CD34+/CD45+/CD38─ CML LSC, CD34+/CD45+/CD38+ CML progenitor cells, CML MNC, sorted CD34+/CD38─ cord blood (CB) SC, CB-derived CD34+/CD38+ progenitor cells, and CB MNC. Total RNA was extracted from sorted cells using RNeasy Micro-Kit (Qiagen) and used (100 ng total RNA) for Gene Chip analyses. Preparation of terminal-labeled cRNA, hybridization to genome-wide human PrimeView GeneChips (Affymetrix, Santa Clara, CA, USA) and scanning of arrays were carried out according to the manufacturer's protocols (https://www.affymetrix.com). Robust Multichip Average (RMA) signal extraction and normalization were performed according to http://www.bioconductor.org/ as described.18 Differences in mRNA expression levels (from multiple paired samples) were calculated as mRNA ratio of i) CML LSC versus CB SC, ii) CML LSC versus CD34+/CD38+ CML progenitors, and normal cord blood SC versus cord blood progenitors. To calculate differential gene expression between individual sample groups where appropriate, we performed a statistical comparison using the LIMMA package as described previously. Briefly, LIMMA estimates the fold change between predefined sample groups by fitting a linear model and using an empirical Bayes method to moderate the standard errors of the estimated log-fold changes for each probe set.
2014-04-17 | E-GEOD-40721 | biostudies-arrayexpress
Project description:Properties of cancer stem cells (CSC) involved in drug-resistance and relapse have significant effect on clinical outcome. Although tyrosine kinase inhibitors (TKIs) have dramatically improved survival of patients with chronic myelogenous leukemia (CML), TKIs have not fully cure CML due to TKI-resistant CML stem cells. Moreover, the relapse after discontinuation of TKIs has not been predicted in CML patients with best TKI-response. In our study, pre-hematoopoietic progenitor cells (pre-HPCs), a model of CML stem cells derived from CML-iPSCs identified a novel antigen of TKI-resistant CML cells. Even in the fraction reported as TKI-sensitive, the antigen+ cells showed TKI-resistance in CML patients. In addition, residual CML cells in patients with optimal TKI-response were concentrated in the antigen+ population.
2016-12-21 | GSE92624 | GEO
Project description:Analysis of lin-CD34+CD45+ (iCD34+) cell population from two normal bone marrow-derived (BM1K and BM9) iPSCs and two CML (CML15 and CML17) iPSCs . CML iCD34+ cells have characteristics similar to primary CML leukemia stem cell in patients. Results provide insight into molecular profile characterized CML iCD34 and mechanism of its maintenance and drug resistance. iCD34+ cell samples obtained from two control BM1K and BM9 iPSCs (both for the same normal donor) and CML15 and CML17 iPSCs (both from the same patient in chronic phase of CML). Each group was treated with DMSO (control) or 5 μM imatinib. The complete phenotype for iCD34+ cells: lin-CD34+CD45+CD90+CD117+CD45RA-. This population also inclyde Rhodaminelow and ALDKhigh cells.
2014-08-31 | E-GEOD-60065 | biostudies-arrayexpress
Project description:This is a class prediction experiment, where the class is the response status to imatinib (also called Gleevec), a drug used to treat patients with chronic myelogenous leukemia (CML). There are two data sets, a training set (from Leipzig, 8 Responders and 5 Non-Responders) and a validation set (from Mannheim, 8 Responders and 7 Non-Responders). The objective is to identify differentially regulated genes between CML patients who respond and those who do not respond to imatinib and confirm the results in the validation data set. The samples from blood or bone marrow of CML patients were hybridized to Affymetrix HG-U95Av2 chip and RMA was used to generate the normalized signal values.
2007-08-25 | E-GEOD-2535 | biostudies-arrayexpress
Project description:Imatinib is highly effective in the treatment of chronic myelogenous leukemia (CML), but the primary and acquired imatinib resistance remains the big hurdle. Molecular mechanisms for CML resistance to tyrosine kinase inhibitors, beyond point mutations in BCR-ABL kinase domain, still need to be addressed. Here, we demonstrated that TXNIP is a novel BCR-ABL target gene. Suppression of TXNIP is responsible for BCR-ABL triggered glucose metabolic reprogramming and mitochondrial homeostasis. Mechanistically, Miz-1/P300 complex transactivates TXNIP through the recognition of TXNIP core promoter region, responding to the c-Myc suppression by either imatinib or BCR-ABL knockdown. TXNIP restoration sensitizes CML cells to imatinib treatment and compromises imatinib resistant CML cell survival, predominantly through the blockage of both glycolysis and glucose oxidation which results in the mitochondrial dysfunction and ATP production. In particular, TXNIP suppresses expressions of the key glycolytic enzyme, HK2 and LDHA, potentially through Fbw7-dependent c-Myc degradation. In accordance, BCR-ABL suppression of TXNIP provides a novel survival pathway for the transformation of mouse BM cells. Combination of drug inducing TXNIP expression with imatinib synergistically kills CML cells from patients and further extends the survival of CML mice. Thus, the activation of TXNIP represents an effective strategy for CML treatment to overcome resistance.
2023-05-03 | GSE218451 | GEO
Project description:Its a mathematical model depicting CML (chronic myelogenous leukemia) interaction with T cells and impact of T cell activations on CML progression over time.
2024-09-02 | BIOMD0000000733 | BioModels