GEO DataSets

(Submitter supplied) To investigate DNA copy number changes in mouse B-cell lymphoma induced by ionizing radiation.

Organism:

Mus musculus

Type:

Genome variation profiling by array

Platform:

GPL19767

9 Samples

Download data: TXT, XLSX

(Submitter supplied) We used microarrays to investigate gene expression changes in tumor-bearing Pax5+/- mice

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6246

17 Samples

Download data: CEL

(Submitter supplied) Hypomorphic mutations of the transcription factor PAX5 occur in one third of B-progenitor acute lymphoblastic leukemias (B-ALLs). To identify PAX5-regulated genes in B-ALL, here we employ inducible expression of PAX5 in a human B-ALL cell line (REH) that harbors a loss-of-function mutation in PAX5. In this model, inducing PAX5 expression is associated with competitive disadvantage.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

2 Samples

Download data: TXT

(Submitter supplied) Hypomorphic mutations of PAX5 occur in one third of B-progenitor acute lymphoblastic leukemias (B-ALLs), however their functional consequences remain undefined. Here we employ advanced transgenic RNAi in mice to suppress endogenous Pax5 expression in the hematopoietic compartment in vivo, which co-operates with activated STAT5 to induce B-ALL. In this model, restoring endogenous Pax5 expression in established B-ALL induces transcriptional and immunophenotypic changes reminiscent of normal B cell differentiation, disabling leukemia-initiating capacity and ultimately causing leukemia clearance.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

6 Samples

Download data: TXT

(Submitter supplied) Triplicate RNA-seq expression analysis of bone marrow pre-B cells isolated from mice, to demonstrate repertoire at the IgH locus

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

3 Samples

Download data: TXT

(Submitter supplied) The adaptor protein LNK (SH2B3) has emerged as an important protein in regulating B cell development B cell leukemia. Loss-of-function mutations in LNK (SH2B3) are found in Philadelphia chromosome–like acute lymphoblastic leukemia (Ph-like ALL), but how LNK regulates normal B cell development or promotes leukemogenesis remains unclear. We found that combined loss of Lnk and tumor suppressors Tp53 in mice triggers a highly aggressive and transplantable precursor B-ALL. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL16570

15 Samples

Download data: CEL

(Submitter supplied) STAT5 is critical for differentiation, proliferation and survival of progenitor B cells suggesting a possible role in Acute Lymphoblastic Leukemia (ALL). Herein, we show increased expression of activated STAT5 in ALL patients, which correlates with treatment outcome. Mutations in Ebf1 and Pax5, genes critical for B cell development have also been identified in human ALL. To determine whether mutations in Ebf1 or Pax5 synergize with STAT5 activation to induce ALL we crossed mice expressing a constitutively active form of STAT5 (Stat5b-CA) with mice heterozygous for Ebf1 or Pax5. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

17 Samples

Download data: CEL

(Submitter supplied) To examine the role of PAX5 alterations in leukemogenesis, we performed mutagenesis screens of mice heterozygous for a loss-of-function Pax5 allele. Both chemical and retroviral mutagenesis resulted in a significantly increased penetrance and reduced latency of leukemia, with a shift to B-lymphoid lineage. We observed a range of maturation of lymphoid tumors, and genomic profiling identified a high frequency of secondary genomic mutations, deletions and retroviral insertions targeting B-lymphoid development, including Pax5, and additional genes and pathways known to be mutated in ALL, including tumor suppressors, Ras and JAK-STAT signaling. more...

Organism:

Mus musculus

Type:

Genome variation profiling by genome tiling array

Platform:

GPL13131

39 Samples

Download data: TXT

(Submitter supplied) A new subtype of B-ALL was identified through integrative genomic analysis and H3K27ac HiChIP was used to investigate impact of structural variants on the CDX2-FLT3-PAN3 genomic region

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL24676

2 Samples

Download data: BEDPE, BW, HIC

(Submitter supplied) We surveyed the DNA methylation levels of 435,941 CpG sites in samples from 764 children at diagnosis of ALL and from 27 children at relapse. This survey uncovered four characteristic methylation signatures. First, compared with control blood cells, the methylomes of ALL cells shared 9,406 predominantly hypermethylated CpG sites, independent of cytogenetic background. Second, each cytogenetic subtype of ALL displayed a unique set of hyper- and hypomethylated CpG sites. more...

Organism:

Homo sapiens

Type:

Methylation profiling by genome tiling array

Platform:

GPL13534

945 Samples

Download data: IDAT, TXT

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

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Other

Platforms:

GPL17021 GPL13112

64 Samples

Download data: VCF

(Submitter supplied) The transcription factors EBF1 and PAX5 are frequently mutated in B cell acute lymphoblastic leukemia (B-ALL). We demonstrate that Pax5+/- x Ebf1+/- compound heterozygous mice develop leukemia with high penetrance. Similar results were seen in Pax5+/- x Ikzf1+/- and Ebf1+/- x Ikzf1+/- mice for B-ALL, or in Tcf7+/- x Ikzf1+/- mice for T cell leukemia. To identify genetic defects that cooperate with Pax5 and Ebf1 compound heterozygosity to initiate leukemia, we carried out a Sleeping Beauty transposon screen. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

53 Samples

Download data: TXT

(Submitter supplied) The transcription factors EBF1 and PAX5 are frequently mutated in B cell acute lymphoblastic leukemia (B-ALL). We demonstrate that Pax5+/- x Ebf1+/- compound heterozygous mice develop leukemia with high penetrance. Similar results were seen in Pax5+/- x Ikzf1+/- and Ebf1+/- x Ikzf1+/- mice for B-ALL, or in Tcf7+/- x Ikzf1+/- mice for T cell leukemia. To identify genetic defects that cooperate with Pax5 and Ebf1 compound heterozygosity to initiate leukemia, we carried out a Sleeping Beauty transposon screen. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL13112

11 Samples

Download data: TXT, VCF

(Submitter supplied) We used microarrays to investigate gene expression changes in leukemic cells from Pax5+/- mice treated with antibiotics. Precursor B cell acute lymphoblastic leukemia (pB-ALL), the most common type of childhood leukemia, is frequently characterized by the cooperation of a genetic predisposition acquired in utero and secondary oncogenic events taking place only in a fraction of predisposed children after birth. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6246

13 Samples

Download data: CEL

(Submitter supplied) PAX5 is a tumor suppressor in B-ALL, while the role of PAX5 fusion proteins in B-ALL development is largely unknown. Here we studied the function of PAX5-ETV6 and PAX5- FOXP1 in mice expressing these proteins from the Pax5 locus. Both proteins arrested Blymphopoiesis at the pro-B-to-pre-B cell transition and, contrary to their proposed dominantnegative role, did not interfere with the expression of most Pax5 target genes. more...

Organism:

Mus musculus

Type:

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

Platforms:

GPL17021 GPL11002 GPL13112

36 Samples

Download data: BW, TXT

(Submitter supplied) The transcription factor STAT5 plays a critical role in B cell acute lymphoblastic leukemia (B-ALL). How STAT5 mediates this effect is unclear. Here we demonstrate that STAT5 activation cooperates with defects in the pre-BCR signaling components encoded by Blnk, Btk, Prkcb, Nfkb1, and Ikzf1 to initiate B-ALL. STAT5 antagonizes NF-κB and IKAROS by opposing regulation of shared target genes. STAT5 binding was enriched at super-enhancers, which were associated with an opposing network of transcription factors, including PAX5, EBF1, PU.1, IRF4, and IKAROS. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

40 Samples

Download data: CEL

(Submitter supplied) While PAX5 is an important tumor suppressor in B-ALL, it is also involved in oncogenic translocations coding for PAX5 fusion proteins. PAX5-JAK2 encodes a protein consisting of the PAX5 DNA-binding region fused to the constitutively active JAK2 kinase domain. Here, we studied the oncogenic function of PAX5-JAK2 in a mouse model expressing it from the endogenous Pax5 locus. The Pax5Jak2/+ mice rapidly developed an aggressive B-ALL in the absence of another cooperating mutation. more...

Organism:

Mus musculus

Type:

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

Platforms:

GPL21103 GPL11002

46 Samples

Download data: BW, TXT

(Submitter supplied) A novel heterozygous germline variant, c.547G>A (p.Gly183Ser), in the paired box protein encoding gene, PAX5, was found to segregate with disease in two unrelated kindreds with autosomal dominant pre-B cell acute lymphoblastic leukemia (ALL). Leukemic cells from both families exhibited 9p deletion, with loss-of-heterozygosity and retention of the mutant PAX5 allele at 9p13. Two additional sporadic ALL cases with 9p loss demonstrated PAX5 Gly183 substitution in the leukemic cells. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL11180

40 Samples

Download data: CEL

(Submitter supplied) We used microarrays to investigate gene expression changes in healthy and leukemic cells from Pax5+/- and IL6+/-;Pax5+/- mice in CF and SPF housing conditions. PAX5 is one of the most frequently mutated genes in B-cell acute lymphoblastic leukemia (B-ALL), and children with inherited preleukemic PAX5 mutations are at a higher risk of developing the disease. Abnormal profiles of inflammatory markers can be detected in neonatal blood spot samples of children who later developed B-cell precursor B-ALL. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6246

22 Samples

Download data: CEL

(Submitter supplied) Xenograft models represent an excellent method for expanding primary leukemias, but their ability to preserve the gene expression profile of the parent leukemia may also depend on providing microenvironmental factors that are not cross-reactive between human and mouse. Here we focused on leukemias with a CRLF2 mutation, and the ability of human TSLP to stimulate these cells.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

5 Samples

Download data: XLSX