Pax5+/- murine model
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB10678 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Infection exposure is a causal factor in B-precursor acute lymphoblastic leukemia as a result of Pax5 inherited susceptibility
| PRJNA264336 | ENA
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
Project description: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. However, how inflammatory signals contribute to B-ALL development is unclear. Here, we demonstrate that Pax5 loss results in the enhanced production of the inflammatory cytokine interleukin-6 (IL-6), which appears to act in an autocrine fashion to promote leukemia growth. In vivo genetic downregulation of IL-6 in Pax5 mutant mice retards B-cell leukemogenesis. In vivo pharmacologic inhibition of IL-6 with a neutralizing IL-6 antibody in Pax5 mutant mice with B-ALL clears leukemic cells. This exciting novel IL 6 signaling paradigm identified in mice was also substantiated in humans. Altogether, our studies establish aberrant IL6 expression caused by Pax5 loss as a hallmark of Pax5-dependent B-ALL and the IL6 as a therapeutic vulnerability for B-ALL characterized by PAX5 loss.
2020-07-17 | GSE154589 | GEO
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
Project description:PAX5, a transcription factor essential for B-cell development, has been found as a frequent target of abnormalities in B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) cases, showing point mutations, deletions, as well as translocations with several partner genes. We identified four novel PAX5 fusion partner genes by performing a screening on BCP-ALL cases with 9p rearrangements. Copy Number Variation analysis of translocated samples showed that few significant cooperative genetic lesions are present in addition to the translocation event, suggesting that it might have a primary role in leukemogenesis.
2015-03-02 | E-MTAB-2416 | biostudies-arrayexpress
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.
2014-04-06 | GSE45834 | GEO
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.
2013-08-01 | GSE45260 | GEO
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
Project description:PAX5-JAK2 has recently been identified as a novel recurrent fusion gene in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) but the function of the encoded chimeric protein has not yet been characterized in detail. Herein we show that the PAX5-JAK2 chimera, which consists of the DNA-binding paired domain of PAX5 and the active kinase domain of JAK2, is a nuclear protein that has the ability to bind to wild-type PAX5 target loci. Moreover, our data provide compelling evidence that PAX5-JAK2 functions as nuclear catalytically active kinase that autophosphorylates and in turn phosphorylates and activates downstream STATs in an apparently non-canonical mode. The chimeric protein also enables cytokine-independent growth of Ba/F3 cells and, therefore, possessing transforming potential. Importantly, the kinase activity of PAX5-JAK2 can be efficiently blocked by JAK2 inhibitors rendering it a potential target for therapeutic intervention. Together, our data show that PAX5-JAK2 simultaneously deregulates the PAX5 downstream transcriptional program and activates the JAK-STAT signaling cascade, and thus, by interfering with these two important pathways, may promote leukemogenesis.
2014-12-29 | GSE56449 | GEO
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