Filters
Technology
Platform
GSE7182
Homo sapiens
4 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The Philadelphia chromosome (Ph) encoding the oncogenic BCR-ABL1 kinase defines a subset of ALL with a particularly unfavorable prognosis. Acute lymphoblastic leukemia (ALL) cells are derived from B cell precursors in most cases and typically carry rearranged immunglobulin heavy chain (IGH) variable (V) region genes devoid of somatic mutations. Somatic hypermutation is restricted to mature germinal center B cells and depends on activation-induced cytidine deaminase (AID). Studying AID expression in 108 cases of ALL, we detected AID mRNA in 24 of 28 Ph-positive ALLs as compared to 6 of 80 Ph-negative ALLs. Forced expression of BCR-ABL1 in Ph-negative ALL cells and inhibition of the BCR-ABL1-kinase showed that aberrant expression of AID depends on BCR-ABL1 kinase activity. Consistent with aberrant AID expression in Ph-positive ALL, IGH V region genes and BCL6 were mutated in many Ph-positive but unmutated in most Ph-negative cases. In addition, AID introduced DNA-single-strand breaks within the tumor suppressor gene CDKN2B in Ph-positive ALL cells, which was sensitive to BCR-ABL1 kinase inhibition and silencing of AID expression by RNA interference. These findings identify AID as a BCR-ABL1-induced mutator in Ph-positive ALL cells, which may be relevant with respect to the particularly unfavorable prognosis of this leukemia subset.
Publication Title
Activation-induced cytidine deaminase acts as a mutator in BCR-ABL1-transformed acute lymphoblastic leukemia cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
We report the gene expression profiles of germinal center B cells obtained by FACS analyses of normal human lymph nodes.
Publication Title
Identification and functional relevance of de novo DNA methylation in cancerous B-cell populations.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In order to investigate the function of Bach2 in pre-B ALL, we isolated bone marrow cells from wildtype and Bach2 knockout mice of C57Bl6 background and transformed them with BCR-ABL1.
Publication Title
Mechanistic rationale for targeting the unfolded protein response in pre-B acute lymphoblastic leukemia.
Sample Metadata Fields
Age, Specimen part, Disease, Disease stage, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Mechanistic rationale for targeting the unfolded protein response in pre-B acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
The plasma cell transcription factor XBP1 is critical for terminal differentiation of B cells into plasma cells but has no known role at earlier stages of B-cell development. Here we show that XBP1 is not only important during early B-cell development and for survival of pre-B cells but also protects pre-B ALL cells. Among pre-B ALL subset, XBP1 was hypomethylated and highest expressed in the Ph+ ALL subset. Cre-mediated deletion of XBP1 in a mouse model of Ph+ ALL compromised proliferation and viability and prolonged survival of leukemia-bearing mice. Interestingly, XBP1 expression levels were positively transcriptionally regulated by STAT5 and negatively by BACH2 and BCL6. High XBP1 expression in high risk ALL patients at the time of diagnosis predicted poor outcome in two clinical trials. Clinically, small-molecule inhibition of IRE1-dependent XBP1-activation caused cell death of patient-derived pre-B ALL cells and affected leukemia-initiation in transplant recipient mice. Collectively, these studies identify XBP1 as an important survival factor and as a potential therapeutic target to overcome drug-resistance in pre-B ALL. Overall design: Genome-wide profiling of mRNA levels in p210 transduced murine Xbp1 fl/+ pre-B cells with ERT2 (XE.1,2,3) and Cre- ERT2 Â (XC.1,2,3).
Publication Title
Mechanistic rationale for targeting the unfolded protein response in pre-B acute lymphoblastic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 1 Downloadable Sample
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The plasma cell transcription factor XBP1 is critical for terminal differentiation of B cells into plasma cells but has no known role at earlier stages of B-cell development. Here we show that XBP1 is not only important during early B-cell development and for survival of pre-B cells but also protects pre-B ALL cells. Among pre-B ALL subset, XBP1 was hypomethylated and highest expressed in the Ph+ ALL subset. Cre-mediated deletion of XBP1 in a mouse model of Ph+ ALL compromised proliferation and viability and prolonged survival of leukemia-bearing mice. Interestingly, XBP1 expression levels were positively transcriptionally regulated by STAT5 and negatively by BACH2 and BCL6. High XBP1 expression in high risk ALL patients at the time of diagnosis predicted poor outcome in two clinical trials. Clinically, small-molecule inhibition of IRE1-dependent XBP1-activation caused cell death of patient-derived pre-B ALL cells and affected leukemia-initiation in transplant recipient mice. Collectively, these studies identify XBP1 as an important survival factor and as a potential therapeutic target to overcome drug-resistance in pre-B ALL.
Publication Title
Mechanistic rationale for targeting the unfolded protein response in pre-B acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
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.
Publication Title
BCL6-mediated repression of p53 is critical for leukemia stem cell survival in chronic myeloid leukemia.
Sample Metadata Fields
Age, Disease, Disease stage
View Samples- Homo sapiens
- 170 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This data was used to determine levels of BRCA1 and BRCA2 in primary human leukemia samples. Samples were determined to be high BRCA1 and/or BRCA2 or low BRCA1 and/or BRAC2.
Publication Title
Personalized synthetic lethality induced by targeting RAD52 in leukemias identified by gene mutation and expression profile.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 67 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
A comparison of global gene expression between rigorously defined stem and progenitor cells from patients with chronic myeloid leukaemia (CML) in chronic (CP), accelerated (AP) and blastic (BC) phase and similar populations isolated from normal volunteers.
Publication Title
Personalized synthetic lethality induced by targeting RAD52 in leukemias identified by gene mutation and expression profile.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Mus musculus, Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
BCOR regulates myeloid cell proliferation and differentiation.
Sample Metadata Fields
Age, Specimen part, Disease, Disease stage
View Samples