GEO DataSets

(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) 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) 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) 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) 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) 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) 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) Total RNA was extracted from Lin-Sca-1+c-Kit+ (LSK) cells sorted from the BM of Spred1HSCΔ/ΔSCLtTA/BCR-ABL (HSC KO) and Spred1HSCwt/wtSCLtTA/BCR-ABL (HSC wt) (n=5 mice per group, both group given 7 doses of 250μg poly(I:C), ip, every two days, to activate Mx1-cre), Spred1ECΔ/ΔSCLtTA/BCR-ABL (EC KO) and Spred1ECwt/wtSCLtTA/BCR-ABL (EC wt) (n=5 mice per group) mice using the miRNeasy micro Kit (Qiagen, Valencia, CA). more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

26 Samples

Download data: TXT

(Submitter supplied) Evidence indicates that chronic myeoid leukemia (CML) stem cells (LSC) persistence is due to bone marrow (BM) niche protection. However, little is known about the underlying molecular mechanisms. We here characterized CML patient BM cellular niches including endothelial cells, mesenchymal stem cells and mature stromal cells that were freshly isolated by fluorescence-activated cell sorting.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

31 Samples

Download data: XLSX

(Submitter supplied) We here by prospectively characterizing BM stormal cells from healthy donors and patients with chornic myeloid leukemia (CML) have found that CXCL14 is dysregulated in CML patient bone marrow niche. Further, CXCL14 promotes TKI therapy response to CML LSCs in vitro and in vivo. To further determine the molecular mechanisms of CXCL14 action, we performed RNA sequencing of CML CD34+CD38- cells 6-24h post stimulation with conditioned media (CM) derived from either NIH3-CTRL or NIH3-CXCL14 cells.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

16 Samples

Download data: XLSX

(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) The family of signal transduction adapter proteins (STAPs) has been reported to be involved in a variety of intracellular signaling and transcriptional molecules. We originally cloned STAP-2 as a c-fms interacting protein and found the effects on chronic myeloid leukemia (CML) leukemogenesis. STAP-2 binds to BCR-ABL, up-regulates BCR-ABL phosphorylation and activates its downstream molecules. In this study, we evaluated the role of STAP-1, another member of the family, in CML pathogenesis. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

2 Samples

Download data: TXT

(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