Gene expression analysis of chronic myeloid leukemic stem cells and progenitor cells from untreated and imatinib-treated CML-like mice
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ABSTRACT:
PROVIDER: PRJNA732068 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14623100.fastq.gz | Fastqsanger.gz | |||
| SRR14623101.fastq.gz | Fastqsanger.gz | |||
| SRR14623102.fastq.gz | Fastqsanger.gz | |||
| SRR14623103.fastq.gz | Fastqsanger.gz | |||
| SRR14623104.fastq.gz | Fastqsanger.gz |
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Project description:To understand gene expression signatures of CML stem cells underlying imatinib-resistance, we compared transcriptomes of CML stem and progenitor cells from vehicle and imatinib-treated CML mice, respectively.
2021-05-23 | GSE175323 | GEO
Project description:Imatinib, as the first-line agent of chronic myeloid leukemia (CML), is ineffective in eradicating CML stem/progenitor cells, thus unable to prevent late relapse. Here we present data indicating that fenretinide preferentially targets CD34+ CML cells and enhances the efficacy of imatinib in CML. As tested by colony forming cell assays, both number and size of total colonies derived from CD34+ CML cells were significantly reduced by fenretinide, and by combining fenretinide with imatinib. In particular, colonies derived from erythroid progenitors and those derived from more primitive pluripotent progenitor cells were highly sensitive to fenretinide/fenretinide plus immtinib. Further data showed that fenretinide was able to induce apoptosis in CD34+ CML cells which were refractory to imatinib. Through transcriptome analysis and followed by molecular validation, we further showed that apoptosis induced by fenretinide in CD34+ CML cells was mediated by complex mechanisms of stress responses, probably triggered by elevated levels of intracellular reactive oxygen species. Thus, fenretinide combines with imatinib may represent a new strategy for the treatment of CML, in which fenretinide targets primitive CD34+ CML cells whereas imatinib targets leukemic blasts. This strategy may eventually reduce the risk of relapse and probably resistant as well in CML patients.
2009-12-01 | GSE17480 | GEO
Project description:Imatinib has become the current standard therapy for patients with chronic myelogenous leukaemia (CML). For a better understanding of the Imatinib-related molecular effects in vivo, we assessed gene expression profiles of Philadelphia Chromosome positive (Ph+) CD34+ cells from peripheral blood of 6 patients with de novo CML in chronic phase. After 7 days of treatment with Imatinib the Ph+ CD34+ cells were reassessed to look for changes in the transcriptome. The expression level of 303 genes was significantly different comparing the transcriptome of the Ph+ CD34+ cells before and after 7 days of Imatinib therapy (183 down-regulated, 120 up-regulated, lower bound ≥1.2-fold). For a substantial number of genes governing cell cycle and DNA replication, the level of expression significantly decreased (CDC2, RRM2, PCNA, MCM4). On the other hand, therapy with Imatinib was associated with an increase of genes related to adhesive interactions, such as L-selectin or CD44. A group of 8 genes with differential expression levels were confirmed using a gene specific quantitative real-time PCR. Thus, during the first week of treatment, Imatinib is preferentially counteracting the bcr-abl induced effects related to a disturbed cell cycle and defective adhesion of leukemic Ph+ CD34+ cells.
2008-07-30 | GSE12211 | GEO
Project description:Imatinib has become the current standard therapy for patients with chronic myelogenous leukaemia (CML). For a better understanding of the Imatinib-related molecular effects in vivo, we assessed gene expression profiles of Philadelphia Chromosome positive (Ph+) CD34+ cells from peripheral blood of 6 patients with de novo CML in chronic phase. After 7 days of treatment with Imatinib the Ph+ CD34+ cells were reassessed to look for changes in the transcriptome. The expression level of 303 genes was significantly different comparing the transcriptome of the Ph+ CD34+ cells before and after 7 days of Imatinib therapy (183 down-regulated, 120 up-regulated, lower bound â¥1.2-fold). For a substantial number of genes governing cell cycle and DNA replication, the level of expression significantly decreased (CDC2, RRM2, PCNA, MCM4). On the other hand, therapy with Imatinib was associated with an increase of genes related to adhesive interactions, such as L-selectin or CD44. A group of 8 genes with differential expression levels were confirmed using a gene specific quantitative real-time PCR. Thus, during the first week of treatment, Imatinib is preferentially counteracting the bcr-abl induced effects related to a disturbed cell cycle and defective adhesion of leukemic Ph+ CD34+ cells. Experiment Overall Design: In total 6 patients with new diagnosis CML (Chronic Myelogenous Leukemia) in chronic phase are inculded in the study. The gene expression profiles of the CD34+ hematopoietic stem and progenitor cells from the patients before first treatment with Glivec (Imatinib) are compared to the gene expression profiles of the CD34+ hematopoietic stem and progenitor cells of the same patients after 7 days of treatment with 400 mg Glivec / day.
2008-10-21 | E-GEOD-12211 | biostudies-arrayexpress
Project description:Imatinib therapy is first-line treatment for chronic myeloid leukemia (CML), and its failure to target CML progenitor/stem cells may lead to an increased risk of relapse. We report here that fenretinide, a well-tolerated vitamin A derivative, is capable of eradicating primitive CML progenitor/stem cells and significantly enhances the efficacy of imatinib at physiologically achievable concentrations. As tested by colony forming cell assays, formation of various colonies derived primitive CML CD34+ cells was significantly suppressed by fenretinide, particularly with respect to the formation of colonies derived from erythroid progenitors and more primitive CML progenitor/stem cells. Also, fenretinide significantly enhanced the ability of imatinib to suppress the formation of the colonies. Moreover, fenretinide was able to induce apoptosis in primitive CML CD34+ cells while sparing the normal counterparts. In particular, primitive CML CD34+CD38- cells appeared to be most sensitive to fenretinide induced apoptosis. Through transcriptome analysis and molecular validation, we further showed that fenretinide induced apoptosis in CML CD34+ cells was probably mediated by a series of stress responsive events which were likely triggered by elevated levels of intracellular reactive oxygen species. Accordingly, the combination of fenretinide and imatinib may provide a potential solution for overcoming relapse and resistance in CML. Experiment Overall Design: Transcriptome profiles of CML CD34+ cells with and without fenretinide treatment were analyzed using whole genome expression arrays (Affymetrix HG-U133 Plus 2.0) in four CML patients (CML32, CML33, CML34 and CML35, see Table 1). To minimize potential data biases, both treated and untreated cell samples were maintained in culture for 48 hours before hybridization.
2009-12-05 | E-GEOD-17480 | biostudies-arrayexpress
Project description:Tyrosine kinase inhibitors (TKIs) are highly effective for treatment of chronic myeloid leukemia (CML), but very few patients are cured. Major drawbacks with TKIs are their low efficacy in eradicating the leukemic stem cells responsible for disease maintenance and relapse upon TKI cessation. Here, we performed RNA-sequencing of flow-sorted primitive (CD34+CD38low) and progenitor (CD34+CD38+) chronic phase CML cells and identified transcriptional upregulation of 32 cell surface molecules relative to corresponding normal bone marrow cells. Focusing on novel markers with increased expression on primitive CML cells, we confirmed upregulation of the scavenger receptor CD36 and the leptin receptor (LEPR) by flow cytometry. We also delineate a subpopulation of primitive CML cells expressing CD36 that is less sensitive to imatinib treatment. Using CD36 targeting antibodies, we show that the CD36 positive cells can be targeted and killed by antibody dependent cellular cytotoxicity (ADCC). In summary, CD36 defines a subpopulation of primitive CML cells with decreased imatinib sensitivity that can be effectively targeted by ADCC using an anti-CD36 antibody.
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Project description:Some chronic myeloid leukemia (CML) patients with complete molecular response (CMR) are considered able to sustain the CMR after imatinib discontinuation (STOP-IM). Mahon et al. reported that among patients with a CMR lasting at least 2 consecutive years, the CMR was sustained in 41% after imatinib discontinuation. To more appropriately identify patients who can safely discontinue imatinib, we assessed the miRNA profiles of CML patients. We compared CML patients who sustained CMR for more than 6 months after discontinuation of imatinib (STOP-IM group) with those who were receiving imatinib with CMR (currently called as UMD: undetermined minimal disease), and with healthy volunteers (controls).
2014-05-15 | GSE47652 | GEO
Project description:Identification of genes in CML patients with predictive value for their primary cytogenetic outcome to imatinib. All samples analyzed were taken just before the start of imatinib treatment. Leukemic patients were treated second-line with imatinib after failure of an interferon-alpha based therapy (first-line regimen).
2006-05-31 | E-MEXP-433 | biostudies-arrayexpress
Project description:An approximately 40% of chronic myeloid leukemia (CML) patients who discontinued imatinib (IM) therapy maintained undetectable minimal residual disease (UMRD) for more than one year (STOP-IM). We set out to examine plasma miRNAs expression in CML patients who could discontinue IM, to seek the possible distinguishable biomarker in STOP-IM CML patients. We compared CML patients who sustained UMRD for more than one year after discontinuation of imatinib (STOP-IM group) with healthy volunteers (controls).
2016-03-31 | GSE75391 | GEO
Project description:An approximately 40% of chronic myeloid leukemia (CML) patients who discontinued imatinib (IM) therapy maintained undetectable minimal residual disease (UMRD) for more than one year (STOP-IM). We therefore set out to examine exosomal miRNAs expression in CML patients who could discontinue IM, to seek the possible distinguishable biomarker in STOP-IM CML patients. We compared CML patients who sustained UMRD for more than one year after discontinuation of imatinib (STOP-IM group) with healthy volunteers (controls).
2016-03-31 | GSE75389 | GEO