Project description:Proteogenomic analysis and genomic profiling, RNA-sequencing, and mass spectrometry-based analysis of High hyperdiploid childhood acute lymphoblastic leukemia.
Project description:Proteogenomic analysis and genomic profiling, RNA-sequencing, and mass spectrometry-based analysis of High hyperdiploid childhood acute lymphoblastic leukemia.
Project description:Development of B-acute lymphoblastic leukemia accompanies with multiple variable mutations. Beside the structural and chromosomal alterations, especially mutations in the regulators of B cell differentiation are common. Around 60% of the B-ALL show deletions of these genes.
Project description:In precursor B-cell acute lymphoblastic leukemia (ALL), whole chromosome uniparental isodisomy (wUPD) occurs almost uniquely in the high hyperdiploid (51-67 chromosomes) (HH) subtype. Comparison of 26 HH with wUPD with 31 with noUPD, showed a higher modal number of chromosomes and gains of 5+ in wUPD. Mutations in genes within epigenetic pathways with upregulation of genes involved in cellular response to stress and stimuli, and mutations in RAS/RTK pathways and upregulation of genes in RNA Polymerase III pathway were seen in wUPD and noUPD respectively. Though overall outcomes were similar in patient with and without wUPD, those with noUPD were more likely to have residual disease after treatment. Differential gene expression between the two groups showed upregulation of genes involved in thiopurine drug resistance in wUPD. Genome-wide differences between HH ALL with and without UPD identified plausible biological explanations for the heterogeneity in therapeutic response in HH ALL.
Project description:BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros. The Philadelphia chromosome, encoding BCR-ABL1, is the defining lesion of chronic myelogenous leukemia (CML) and a subset of acute lymphoblastic leukemia (ALL) cases. To define oncogenic lesions that cooperate with BCR-ABL1 to induce ALL, we performed genome-wide analysis of leukemic samples from 23 CML cases and 304 ALL cases, including 43 BCR-ABL1 B-ALL cases. IKZF1 (encoding the transcription factor Ikaros) was deleted in 83.7% of BCR-ABL1 B-ALL cases, but not in chronic phase CML. Deletion of IKZF1 was also identified as an acquired lesion in lymphoid blast crisis of CML. The IKZF1 deletions resulted in haploinsufficiency, expression of a dominant negative Ikaros isoform or the complete loss of Ikaros expression. Sequencing of IKZF1 deletion breakpoints suggested that aberrant V(D)J recombination is responsible for the deletions. These findings suggest that genetic lesions resulting in the loss of Ikaros function are a key event in the development of BCR-ABL1 ALL. *** Due to privacy concerns, the primary SNP array data is no longer available with unrestricted access. Individuals wishing to obtain this data for research purposes may request access using the Web links below. *** This SuperSeries is composed of the SubSeries listed below.