Expression analysis of BCR/ABL expressing Kit+ cells derived from wild type and ROSACreERT2c-Fosfl/flDusp1-/- bone marrow cells by RNA seq
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE75242 | GEO | 2017/03/20
SECONDARY ACCESSION(S): PRJNA302877
REPOSITORIES: GEO
Similar Datasets
Project description:Using a mouse model of chronic myelogenous leukemia (CML), here we report that HIF1α plays a crucial role in survival maintenance of leukemia stem cells (LSCs). Deletion of HIF1α impairs the propagation of CML through impairing cell cycle progression and inducing apoptosis of LSCs. Deletion of HIF1α results in elevated expression of p16Ink4a and p19Arf in LSCs, and knockdown of p16Ink4a and p19Arf rescues the defective colony-forming ability of HIF1α-/- LSCs. To further identify the pathways in which Hif1a regulates function of LSCs, we performed a comparative DNA microarray analysis using total RNA isolated from BCR-ABL-expressing wild type LSCs and BCR-ABL-expressing Hif1a-/- LSCs. The result was validated by quantitative real-time PCR analysis of non-BCR-ABL-expressing Lin-Sca-1+c-Kit+ cells, BCR-ABL-expressing wild type LSCs, and BCR-ABL-expressing Hif1a-/- LSCs.
2012-04-04 | GSE35111 | GEO
Project description:We previously demonstrated that Alox5 deficiency impairs the function of LSCs and prevents the initiation of BCR-ABL-induced CML. To identify the pathways in which Alox5 gene regulates function of LSCs, we performed a comparative DNA microarray analysis using total RNA isolated from non-BCR-ABL-expressing Lin-Sca-1+c-Kit+, BCR-ABL-expressing wild type LSCs and BCR-ABL-expressing Alox5-/- LSCs. The result was validated by quantitative real-time PCR analysis of non-BCR-ABL-expressing Lin-Sca-1+c-Kit+, BCR-ABL-expressing wild type LSCs and BCR-ABL-expressing Alox5-/- LSCs. We have shown that Alox5 is a critical regulator of leukemia stem cells (LSCs) in a BCR-ABL-induced chronic myeloid leukemia (CML) mouse model, and we hypothesize that the Alox5 pathway represents a major molecular network that regulates LSC function. Therefore, we sought to further dissect this pathway by comparing the gene expression profiles of wild type and Alox5-/- LSCs derived from our mouse model for BCR-ABL-induced CML. DNA microarray analysis revealed a small group of candidate genes that exhibited changes in the levels of transcription in the absence of Alox5 expression. In particular, we noted that the expression of the Msr1 gene was up-regulated in Alox5-/- LSCs, suggesting that Msr1 might suppress the proliferation of LSCs. Using our CML mouse model, we show that Msr1 is down-regulated by BCR-ABL and this down-regulation is partially restored by Alox5 deletion, and that Msr1 deletion causes acceleration of CML development. Moreover, Msr1 deletion markedly increases LSC function through its effects on cell cycle progression and apoptosis. We also show that Msr1 affects CML development by regulating the PI3K-AKT pathway and β-Catenin. Together, these results demonstrate that Msr1 suppresses LSCs and CML development. The enhancement of Msr1 function may be of significance in the development of novel therapeutic strategies targeting CML.
2011-05-17 | GSE29347 | GEO
Project description:One of the main objective of this study is to characterize Imatinib induced MSCs-mediated resistance evolution in BCR-ABL+ ALL. Tyrosine kinase inhibitor (TKI) Imatinib (IM) is used as a frontline therapy for BCR-ABL–positive (BCR-ABL+) acute lymphoblastic leukemia (ALL). However, resistance to IM therapy develops rapidly in a substantial proportion of treated patients, and the molecular mechanisms underlying the resistance are poorly understood. In this study, we identified a novel cascade of consequential events that are initiated by IM, which traverse through mesenchymal stem/stromal cells (MSCs) to leukemic cells, and lead to IM resistance. Our data showed that MSCs exposed to IM were decreased in their stemness and acquired a new functional status that enabled the formation of leukemic cell niches. These MSCs had increased expression of genes encoding chemo-attractants, adhesion molecules, and pro-survival stimulant growth factors. We found that BCR-ABL+ leukemic cells persistently exposed to IM were able to switch from BCR-ABL–driven signaling to growth factor–driven signaling for survival, and this switch was reversible. Blocking both the BCR-ABL–driven pathway and the growth factor–driven JAK pathway effectively eradicated the leukemic cell niches. Our findings illustrate TKI-induced, MSC-mediated drug resistance, suggesting an effective way to eliminate this type of drug resistance in patients with BCR-ABL+ ALL.
2015-09-01 | GSE56472 | GEO
Project description:We previously demonstrated that Alox5 deficiency impairs the function of LSCs and prevents the initiation of BCR-ABL-induced CML. To identify the pathways in which Alox5 gene regulates function of LSCs, we performed a comparative DNA microarray analysis using total RNA isolated from non-BCR-ABL-expressing Lin-Sca-1+c-Kit+, BCR-ABL-expressing wild type LSCs and BCR-ABL-expressing Alox5-/- LSCs. The result was validated by quantitative real-time PCR analysis of non-BCR-ABL-expressing Lin-Sca-1+c-Kit+, BCR-ABL-expressing wild type LSCs and BCR-ABL-expressing Alox5-/- LSCs. We have shown that Alox5 is a critical regulator of leukemia stem cells (LSCs) in a BCR-ABL-induced chronic myeloid leukemia (CML) mouse model, and we hypothesize that the Alox5 pathway represents a major molecular network that regulates LSC function. Therefore, we sought to further dissect this pathway by comparing the gene expression profiles of wild type and Alox5-/- LSCs derived from our mouse model for BCR-ABL-induced CML. DNA microarray analysis revealed a small group of candidate genes that exhibited changes in the levels of transcription in the absence of Alox5 expression. In particular, we noted that the expression of the Msr1 gene was up-regulated in Alox5-/- LSCs, suggesting that Msr1 might suppress the proliferation of LSCs. Using our CML mouse model, we show that Msr1 is down-regulated by BCR-ABL and this down-regulation is partially restored by Alox5 deletion, and that Msr1 deletion causes acceleration of CML development. Moreover, Msr1 deletion markedly increases LSC function through its effects on cell cycle progression and apoptosis. We also show that Msr1 affects CML development by regulating the PI3K-AKT pathway and ?-Catenin. Together, these results demonstrate that Msr1 suppresses LSCs and CML development. The enhancement of Msr1 function may be of significance in the development of novel therapeutic strategies targeting CML. To identify genes that are regulated by BCR-ABL in LSCs and LSCs without Alox5 gene, we compared the gene profile between wild type(WT) LSCs or Alox5-/- LSCs.
2011-05-17 | E-GEOD-29347 | biostudies-arrayexpress
Project description:Using a mouse model of chronic myelogenous leukemia (CML), here we report that HIF1M-NM-1 plays a crucial role in survival maintenance of leukemia stem cells (LSCs). Deletion of HIF1M-NM-1 impairs the propagation of CML through impairing cell cycle progression and inducing apoptosis of LSCs. Deletion of HIF1M-NM-1 results in elevated expression of p16Ink4a and p19Arf in LSCs, and knockdown of p16Ink4a and p19Arf rescues the defective colony-forming ability of HIF1M-NM-1-/- LSCs. To further identify the pathways in which Hif1a regulates function of LSCs, we performed a comparative DNA microarray analysis using total RNA isolated from BCR-ABL-expressing wild type LSCs and BCR-ABL-expressing Hif1a-/- LSCs. The result was validated by quantitative real-time PCR analysis of non-BCR-ABL-expressing Lin-Sca-1+c-Kit+ cells, BCR-ABL-expressing wild type LSCs, and BCR-ABL-expressing Hif1a-/- LSCs. To identify genes that are regulated by BCR-ABL in LSCs and LSCs without the Hif1a gene, we compared the gene profile between wild type (WT) LSCs and Hif1a-/- LSCs.
2012-04-03 | E-GEOD-35111 | biostudies-arrayexpress
Project description:Using BCR-ABL-induced chronic myeloid leukemia (CML) as a disease model for leukemia stem cells (LSCs), we showed that BCR-ABL down-regulates the B lymphoid kinase (Blk) gene in leukemia stem cells in CML mice and that Blk functions as a tumor suppressor in LSCs and suppresses LSC function. Inhibition of this Blk pathway accelerates CML development, whereas increased activity of the Blk pathway delays CML development. To identify the pathways in which Blk regulates function of LSCs, we performed a comparative DNA microarray analysis using total RNA isolated from non-BCR-ABL-expressing Lin-Sca-1+c-Kit+, BCR-ABL- and BCR-ABL-Blk expressing LSCs. This analysis revealed a large group of candidate genes that exhibited changes in the levels of transcription in the Blk expressing LSCs, and uncovered the molecular mechanisms by which Blk suppresses LSCs and CML development.
2012-07-06 | GSE36096 | GEO
Project description:One of the main objective of this study is to characterize Imatinib induced MSCs-mediated resistance evolution in BCR-ABL+ ALL. Tyrosine kinase inhibitor (TKI) Imatinib (IM) is used as a frontline therapy for BCR-ABL–positive (BCR-ABL+) acute lymphoblastic leukemia (ALL). However, resistance to IM therapy develops rapidly in a substantial proportion of treated patients, and the molecular mechanisms underlying the resistance are poorly understood. In this study, we identified a novel cascade of consequential events that are initiated by IM, which traverse through mesenchymal stem/stromal cells (MSCs) to leukemic cells, and lead to IM resistance. Our data showed that MSCs exposed to IM were decreased in their stemness and acquired a new functional status that enabled the formation of leukemic cell niches. These MSCs had increased expression of genes encoding chemo-attractants, adhesion molecules, and pro-survival stimulant growth factors. We found that BCR-ABL+ leukemic cells persistently exposed to IM were able to switch from BCR-ABL–driven signaling to growth factor–driven signaling for survival, and this switch was reversible. Blocking both the BCR-ABL–driven pathway and the growth factor–driven JAK pathway effectively eradicated the leukemic cell niches. Our findings illustrate TKI-induced, MSC-mediated drug resistance, suggesting an effective way to eliminate this type of drug resistance in patients with BCR-ABL+ ALL. Gene expression signatures were compared from triplicate samples of MSCs that were either treated with vehicle or imatinib for 32, 64 and 96 hours.
2015-09-01 | E-GEOD-56472 | biostudies-arrayexpress
Project description:To gain insight into how miR-142 deficit drives a BC-like transformation, we performed RNA-seq on bone marrow (BM) Lin-Sca-1+c-Kit+ cells (LSKs) harvested from normal miR-142+/+ (wt) and miR-142−/− (miR-142 KO) mice, as well as from leukemic miR-142+/+ BCR-ABL (CP CML) and miR-142−/− BCR-ABL (BC CML) mice, two weeks after BCR-ABL induction. We then performed gene expression profiling analysis using data obtained from RNA-seq of 24 samples of LSK cells from 4 mouse strains (KO vs WT, KO CML vs CML).
2022-11-01 | GSE216794 | GEO
Project description:Chronic myelogenous leukemia (CML) is a malignant disease of the hematopoietic stem cell, characterized by the expression of the Bcr-Abl oncogene by leukemic cells. In order to analyze the molecular pathways modulated by Bcr-Abl, we have previously generated an inducible model of Bcr-Abl expression in the murine Ba/F3 cell line based on the Tet-OFF system. In the present study, through a microarray approach applied to cells grown with (Bcr-Abl-expression OFF) or without (Bcr-Abl-expression ON) doxycycline, a tetracycline analogue, we analyzed the gene expression variations upon Bcr-Abl expression. Keywords: repeat sample
2005-05-01 | GSE1429 | GEO
Project description:Using BCR-ABL-induced chronic myeloid leukemia (CML) as a disease model for leukemia stem cells (LSCs), we showed that BCR-ABL down-regulates the B lymphoid kinase (Blk) gene in leukemia stem cells in CML mice and that Blk functions as a tumor suppressor in LSCs and suppresses LSC function. Inhibition of this Blk pathway accelerates CML development, whereas increased activity of the Blk pathway delays CML development. To identify the pathways in which Blk regulates function of LSCs, we performed a comparative DNA microarray analysis using total RNA isolated from non-BCR-ABL-expressing Lin-Sca-1+c-Kit+, BCR-ABL- and BCR-ABL-Blk expressing LSCs. This analysis revealed a large group of candidate genes that exhibited changes in the levels of transcription in the Blk expressing LSCs, and uncovered the molecular mechanisms by which Blk suppresses LSCs and CML development. Bone marrow cells were transduced with GFP, BCR-ABL-GFP or BCR-ABL-Blk-GFP, followed by transplantation into recipient mice. Fourteen days after transplantation, bone marrow cells were isolated and LSCs were sorted by FACS for isolation of total RNA for DNA microarray analysis.
2012-07-05 | E-GEOD-36096 | biostudies-arrayexpress