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Reduction in Pax5 activity drives ionizing radiation-mediated B-cell acute lymphoblastic leukemia development by modulating DNA-damage response

ABSTRACT: We used microarrays to investigate gene expression changes in tumor-bearing Pax5+/- IR and WT-IR mice. We also analyze gene expression changes in preleukemic Pax5+/- IR and WT-IR mice

ORGANISM(S): Mus musculus

PROVIDER: GSE130667 | GEO | 2019/05/04

REPOSITORIES: GEO

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Germline Aberrations of PAX5 Cause Susceptibility to pre-B cell Acute Lymphoblastic Leukemia

Project description: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. Functional and gene expression analysis of the PAX5 germline variants demonstrated reduced transcriptional activity. These data extend the role of PAX5 alterations in the pathogenesis of pre-B ALL, and implicate PAX5 in a novel syndrome of germline susceptibility to pre-B cell neoplasia. We analyzed 10 samples of J558 murine myeloma cells infected with MSCV-Puro-IRES-GFP (PIG) empty vector (EV; three independent replicates), MSCV-PIG Pax5 WT (WT; three independent replicates), and MSCV-PIG Pax5 G183S (Mut; four independent replicates). Cells were selected with puromycin after infection for 5-7 days, subsequently cells were sorted for GFP and IgM expression by FACS.

2014-04-06 | E-GEOD-45834 | biostudies-arrayexpress

Reduction in Pax5 activity drives ionizing radiation-mediated B-cell acute lymphoblastic leukemia development by modulating DNA-damage response

Project description:Reduction in Pax5 activity drives ionizing radiation-mediated B-cell acute lymphoblastic leukemia development by modulating DNA-damage response

| PRJNA540937 | ENA

Pax5 drives the metabolic shift in the development of pB-ALL as a result of BCR/ABLp190 susceptibility

Project description:We used microarrays to investigate gene expression changes in tumor-bearing Sca1-BCR/ABLp190 and Sca1-BCR/ABLp190+Pax5+/- mice. We also analyze gene expression changes in preleukemic Sca1-BCR/ABLp190 and Sca1-BCR/ABLp190+Pax5+/- mice

2016-08-16 | GSE85600 | GEO

Inducible PAX5 expression in a human B lymphoblastic leukemia cell line

Project description: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. Comparison of REH cell lines with Dox-inducible expression of PAX5-IRES-GFP, or control GFP alone. GFP positive cells were isolated by FACS.

2014-06-18 | E-GEOD-57480 | biostudies-arrayexpress

Infection exposure is a causal factor in B-precursor acute lymphoblastic leukemia as a result of Pax5 inherited susceptibility

Project description:We used microarrays to investigate gene expression changes in tumor-bearing Pax5+/- mice Tumor-bearing bone marrows of three Pax5+/- mice compared with B220+ bone marrow B cells from five WT mice

2014-10-21 | E-GEOD-62529 | biostudies-arrayexpress

Inducible PAX5 expression in a human B lymphoblastic leukemia cell line

2014-06-18 | GSE57480 | GEO

Germline Aberrations of PAX5 Cause Susceptibility to pre-B cell Acute Lymphoblastic Leukemia

Project description: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. Functional and gene expression analysis of the PAX5 germline variants demonstrated reduced transcriptional activity. These data extend the role of PAX5 alterations in the pathogenesis of pre-B ALL, and implicate PAX5 in a novel syndrome of germline susceptibility to pre-B cell neoplasia. We analyzed 40 samples comprising sevenfold replicates of transductions with empty vector, wild type PAX5 and 4 mutant PAX5 constructs

2013-08-01 | E-GEOD-45260 | biostudies-arrayexpress

Molecular role of the PAX5-ETV6 oncoprotein in promoting B cell acute lymphoblastic leukemia

Project description: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. Pax5-Etv6, but not Pax5-Foxp1, cooperated with loss of the Cdkna2a/b tumor suppressor in promoting B-ALL development. Regulated Pax5-Etv6 target genes identified in these B-ALLs encode proteins implicated in pre-BCR signaling and migration/adhesion, which could contribute to the proliferation, survival and tissue infiltration of leukemic B-cells. Together with similar observations made in human PAX5-ETV6+ B-ALLs, these data identified PAX5-ETV6 as a potent oncoprotein. 36 samples in total: A) 24 RNA-Seq samples in 5 cell types: pro-B (5 genotypes, 2-4 replicates) large pre-B (2 genotypes, 2 replicates each) small pre-B (1 genotype, 2 replicates) lymph node (1 genotype, 3 replicates) bone marrow (1 genotype, 2 replicates) B) 12 ChIP-Seq samples in 2 cell types: pro-B (H3K27me3, H3K9ac, H3K4me2, H3K4me3, H3K27ac, 1 replicate each; Pax5Etv6 ChIP, Prd ChIP, 2 replicates each; Pax5 ChIP 1 replicate) lymph node (1 genotype, 2 replicates).

2016-07-30 | E-GEOD-84987 | biostudies-arrayexpress

Molecular role of the PAX5-ETV6 oncoprotein in promoting B cell acute lymphoblastic leukemia

2017-02-06 | GSE84987 | GEO

Affymetrix SNP6.0 array data for PAX5 amplified acute lymphoblastic leukemia

Project description:Intragenic PAX5 amplification in <1%of B-cell precursor acute lymphoblastic leukaemia. Affymetrix SNP 6.0 array analysis was undertaken in patients who showed amplication of PAX5 by MLPA testing using the P335-IKZF1 MLPA kit (www.mlpa.com, MRC Holland, The Netherlands)

2017-06-09 | GSE99813 | GEO

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