GEO DataSets

(Submitter supplied) Tyrosine kinase inhibitors (TKIs) have revolutionized chronic myelogenous leukemia (CML) management. Disease eradication, however, is hampered by innate resistance of leukemia initiating cells (LICs) to TKI-induced killing, which also provides the basis for subsequent emergence of TKI-resistant mutants. We report that EZH2, the catalytic subunit of Polycomb Repressive Complex 2 (PRC2), is overexpressed in CML LICs, required for colony formation, and survival and cell cycle progression of CML cell lines. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL8321

8 Samples

Download data: CEL

(Submitter supplied) Recent studies point to a pivotal role of polycomb repressive complex 2 (PRC2) in stem cell function and cancer. Loss of function approaches targeting individual PRC2 subunits have however generated findings that are difficult to reconcile. Here, we prevent assembly of both Ezh1- and Ezh2-containing PRC2 complexes by conditional deletion of Eed, a core subunit, and assess glodbal gene expression changs in LT-HSCs.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL8321

6 Samples

Download data: CEL

(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) 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 investigate the effect of VDR in the regulation of K562 cells. We then performed gene expression profiling analysis using data obtained from RNA-seq of 2 different cells.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

6 Samples

Download data: XLSX

(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) In this study, we show that targeted deletion of CXCL12 from mesenchymal stromal cells (MSC) reduces normal HSC numbers, but in contrast expands murine LSC numbers by increasing self-renewing cell divisions, related to enhanced EZH2 activity. CML development leads to emergence of abnormal niches of MSC and LSC clusters that are lost upon CXCL12 deletion. Importantly, CXCL12 deletion from MSC also increases LSC elimination by TKI treatment. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

12 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

Analysis of CML cell lines (KU-812, KCL-22, and JURL-MK1) treated with tyrosine kinase inhibitor imatinib. Imatinib inhibits oncogenic BCR-ABL1, a tyrosine kinase present in most CML patients. Results provide insight into molecular mechanisms underlying imatinib inhibition of CML.

Organism:

Homo sapiens

Type:

Expression profiling by array, count, 2 agent, 3 cell line sets

Platform:

GPL570

Series:

GSE24493

6 Samples

Download data: CEL

(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) 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) BCR-ABL1-targeting tyrosine kinase inhibitors (TKIs) have revolutionized treatment of Philadelphia chromosome-positive (Ph+) hematologic neoplasms. Nevertheless, acquired TKI resistance remains a major problem in chronic myeloid leukemia (CML), and TKIs are less effective against Ph+ B-cell acute lymphoblastic leukemia (B-ALL). GAB2, a scaffolding adaptor that binds and activates SHP2, is essential for leukemogenesis by BCR-ABL1, and a GAB2 mutant lacking SHP2 binding cannot mediate leukemogenesis. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

16 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL15520 GPL18573

8 Samples

Download data: BW, TXT

(Submitter supplied) Multiple myeloma (MM) is a hematological malignancy caused by accumulation of abnormal clonal plasma cells. Despite the recent development of novel therapies, relapse of MM eventually occurs due to a remaining population of drug-resistant myeloma stem cells. Side population (SP) cells exhibit cancer stem cell-like characteristics in MM; thus targeting these cells is a promising strategy to completely cure this malignancy. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL15520

4 Samples

Download data: BW

(Submitter supplied) Multiple myeloma (MM) is a hematological malignancy caused by accumulation of abnormal clonal plasma cells. Despite the recent development of novel therapies, relapse of MM eventually occurs due to a remaining population of drug-resistant myeloma stem cells. Side population (SP) cells exhibit cancer stem cell-like characteristics in MM; thus targeting these cells is a promising strategy to completely cure this malignancy. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

4 Samples

Download data: TXT