GEO DataSets

(Submitter supplied) ABL1 kinase inhibitors such as imatinib mesylate (IM) are effective in managing chronic myelogenous leukemia (CML) but incapable of eliminating leukemia stem cells (LSCs), suggesting that kinase−independent pathways support LSC survival. Given that the bone marrow hypoxic microenvironment supports hematopoietic stem cells, we investigated if hypoxia similarly contributes to LSC persistence. Importantly, we found that while BCR−ABL1 kinase remained effectively inhibited by IM under hypoxia, apoptosis became partially suppressed. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

24 Samples

Download data: TXT

(Submitter supplied) 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. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL15207

10 Samples

Download data: CEL

(Submitter supplied) We show the molecular and functional characterization of a novel population of lineage-negative CD34-negative (Lin- CD34-) hematopoietic stem cells (HSCs) from chronic myelogenous leukemia (CML) patients at diagnosis. Molecular caryotyping and quantitative analysis of BCR/ABL transcript demonstrated that about one third of CD34- was leukemic. CML CD34- cells showed kinetic quiescence and limited clonogenic capacity. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL8300

6 Samples

Download data: CEL, CHP

(Submitter supplied) Lin-CD34+CD38+ and Lin-CD34-CD38- cells were isolated from 5 CML patients at diagnosis and 4 healthy donors.

Organism:

Homo sapiens

Type:

Expression profiling by RT-PCR

Platform:

GPL19066

18 Samples

Download data: TXT

(Submitter supplied) Tyrosine kinase inhibitors (TKI) are highly effective in treatment of chronic myeloid leukemia (CML) but do not eliminate leukemia stem cells (LSC), which remain a potential source of relapse. TKI treatment effectively inhibits BCR-ABL kinase activity in CML LSC, suggesting that additional kinase-independent mechanisms contribute to LSC preservation. We investigated whether signals from the bone marrow (BM) microenvironment protect CML LSC from TKI treatment. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Dataset:

GDS4756

Platform:

GPL6244

12 Samples

Download data: CEL

Analysis of CML cells treated with tyrosine kinase inhibitor (TKI) imatinib and BM mesenchymal stromal cells (MSCs). Coculture with MSCs protects the CML cells from TKI-mediated cell death and depletion. Results provide insight into microenvironmental protection of CML cells from TKI treatment.

Organism:

Homo sapiens

Type:

Expression profiling by array, transformed count, 4 protocol, 2 tissue sets

Platform:

GPL6244

Series:

GSE43225

12 Samples

Download data: CEL

(Submitter supplied) We investigated the ability of HDAC inhibitors (HDACi) to target CML stem cells. Treatment with HDACi combined with IM effectively induced apoptosis in quiescent CML progenitors resistant to elimination by IM alone, and eliminated CML stem cells capable of engrafting immunodeficient mice. In vivo administration of HDACi with IM markedly diminished LSC in a transgenic mouse model of CML. The interaction of IM and HDACi inhibited genes regulating hematopoietic stem cell maintenance and survival. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Dataset:

GDS4047

Platform:

GPL570

12 Samples

Download data: CEL

Analysis of sorted chronic myelogenous leukemia (CML) CD34+CD38- cells cultured with histone deacetylase inhibitor analog LBH589 (LBH) and/or BCR-ABL tyrosine kinase inhibitor imatinib mesylate (IM). Results provide insight into molecular mechanisms underlying treatment of CML with LBH and IM.

Organism:

Homo sapiens

Type:

Expression profiling by array, transformed count, 4 agent sets

Platform:

GPL570

Series:

GSE20876

12 Samples

Download data: CEL

(Submitter supplied) 33 miRNAs significantly decreased and 75 miRNAs significantly increased in BCR-ABL+ LSK compared with BCR-ABL- LSK cells, suggesting distinct BCR-ABL-dependent mechanisms of microRNA regulation.

Organism:

Mus musculus

Type:

Non-coding RNA profiling by high throughput sequencing

Platform:

GPL17021

4 Samples

Download data: TXT

(Submitter supplied) A comparison between parental K562 cells (CML) and two clones derived from this cell line : ImaR and PDR which are resistant against Imatinib mesylate and PD166326 respectively , two inhibitors of BCR-ABL. Keywords: gene expression, comparison

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL1456

6 Samples

Download data: GPR

(Submitter supplied) The biology of chronic myeloid leukemia (CML)-stem cells is still incompletely understood. Therefore, we previously developed an inducible transgenic mouse model in which stem cell targeted induction of BCR-ABL expression leads to chronic phase CML-like disease. Here, we now demonstrate that the disease is transplantable using BCR-ABL positive LSK cells (lin-Sca-1+c-kit+). Interestingly, the phenotype is enhanced when unfractionated bone marrow (BM) cells are transplanted. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

6 Samples

Download data: DAT

(Submitter supplied) 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.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

12 Samples

Download data: TXT

(Submitter supplied) Aberrant long noncoding RNA (lncRNA) expression has been described in many human malignancies, including leukemia. Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) is a stem cell disease induced by Bcr-Abl hybrid gene. Here we attempt to identify lncRNAs associated with CML by analyzing lncRNA expression profiles in K562 cells when Bcr-Abl gene silenced. LncRNA microarray analysis revealed a group of lncRNAs that exhibit Bcr-Abl-dependent expression. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL14715

6 Samples

Download data: CALLS, PAIR

(Submitter supplied) 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. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

9 Samples

Download data: XLSX

(Submitter supplied) Leukemia stem cells (LSC) are not eradicated in chronic myeloid leukemia (CML) patients responding to tyrosine kinase inhibitor treatment. Bone marrow (BM) mesenchymal niches play an essential role in hematopoietic stem cell (HSC) maintenance. Here, we examined leukemia-induced alterations in mesenchymal progenitor populations using a murine CML model. 6C3+ stroma-forming progenitors were increased in CML BM, and demonstrated enhanced LSC but reduced HSC support compared to their normal counterparts. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

32 Samples

Download data: XLSX

(Submitter supplied) We identified the BCL6 protooncogene as a critical downstream effector of FoxO3A in self-renewal signaling of CML-initiating cells. BCL6 represses Arf and p53 in CML cells and is required for leukemia stem cell maintenance, colony formation and initiation of leukemia in transplant recipients. Importantly, peptide inhibition of BCL6 in human CML cells compromises colony formation and leukemia-initiation in xenotransplanted mouse recipients. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL10999

2 Samples

Download data: BED, TXT, WIG

(Submitter supplied) In order to investigate the function of STAT5 in ALL, we isolated bone marrow cells from STAT5 fl/fl mice and transformed them with BCR-ABL1. In a second transduction the BCR-ABL1 driven pre-B cells were transformed either with CRE-GFP or empty vector control (GFP) and subjected to gene expression analysis.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6246

6 Samples

Download data: CEL

(Submitter supplied) To identify differences in the gene regulation between BCL6+/+ and BCL6-/- CML cells a gene expression analysis has been performed. We investigated the gene expression pattern in BCL6+/+ cells in the presence or absence of Imatinib and a combination of Imatinib and RI-BPI (a novel retro-inverso BCL6 peptide inhibitor). In BCL6-/- CML cells, we investigated the gene expression pattern in the presence or absence of Imatinib. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

10 Samples

Download data: CEL

(Submitter supplied) The Philadelphia chromosome (Ph) encodes the oncogenic BCR-ABL1 tyrosine kinase, which is present in almost every patient with chronic myeloid leukemia. In this study, the tyrosine kinase inhibitor Imatinib was used for pharmacological inhibition of BCR-ABL1. Gene expression profiles of CML cell lines were analyzed in response to Imatinib treatment.

Organism:

Homo sapiens

Type:

Expression profiling by array

Dataset:

GDS4177

Platform:

GPL570

6 Samples

Download data: CEL

(Submitter supplied) To elucidate the mechanism of BCL6-mediated pre-B cell survival signaling, we investigated the gene expression pattern in BCR-ABL1-transformed BCL6+/+ and BCL6-/- B cell precursors. Pharmacological inhibition of BCR-ABL1 was performed with the BCR-ABL1 kinase inhibitor STI571 (Imatinib).

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

12 Samples

Download data: CEL