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:Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, and it has a 5-year survival rate of 85% for European children. But for subsets of patients who fail to respond to standard of care chemotherapeutics, treatment options are limited, and clinical prognosis is poor. To establish a platform and methodology to better characterize ALL subtypes and identify their pharmacologic vulnerabilities, we assembled a biobank of 49 readily available childhood ALL cell lines representing diverse immunotypes and genetic profiles. Using these cell lines, we performed comprehensive multi-omic analyses, providing proteomic, transcriptomic and pharmacoproteomic characterization of childhood ALL. We used this resource to characterize the functional impact of genetic fusions and cellular differentiation states on the proteome. Additionally, we identified a novel drug vulnerability in one of the ALL subtypes. Our results are provided as an interactive online data portal with navigable proteomics, transcriptomics, and drug sensitivity profiles.
Project description:Gene expression profiling in leukemia cases may predict the clinical outcome of the patients and may improve the treatment for specific leukemia subtypes. The goal is to compare the differences in gene expression pattern between T-ALL and B-ALL subtypes in Malaysian childhood acute lymphoblastic leukemia patients.
Project description:We analyzed 52 Diagnostic samples from childhood Acute lymphoblastic leukemia samples We compared methylation profiles with four ALL cytogentic subtypes using (n=26) long term remission vs. (n=26) that went on to relapse
Project description:We identified germline single nucleotide polymorphisms (SNPs) associated with childhood acute lymphoblastic leukemia (ALL) and its subtypes. Using the Affymetrix 500K Mapping array and publicly available genotypes, we identified 18 SNPs whose allele frequency differed (P<1x10-5) between a pediatric ALL population (n=317) and non-ALL controls (n=17,958). Six of these SNPs differed (P≤0.05) in allele frequency among four ALL subtypes. Two SNPs in ARID5B not only differed between ALL and non-ALL groups (rs10821936, P=1.4x10-15, odds ratio[OR]=1.91; rs10994982, P=5.7x10-9, OR=1.62) but also distinguished B-hyperdiploid ALL from other subtypes (rs10821936, P=1.62 x10-5, OR=2.17; rs10994982, P=0.003, OR 1.72). These ARID5B SNPs also distinguished B-hyperdiploid ALL from other subtypes in an independent validation cohort (n=124 children with ALL) (P=0.003 and P=0.0008, OR 2.45 and 2.86, respectively) and were associated with methotrexate accumulation and gene expression pattern in leukemic lymphoblasts. We conclude that germline genomic variations affect susceptibility to and characteristics of specific ALL subtypes. We used microarrays to detail the global program of gene expression in primary leukemic blasts cells from children diagnosed with acute lymphoblastic leukemia.
Project description:Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, and it has a 5-year survival rate of 85% for European children. But for subsets of patients who fail to respond to standard of care chemotherapeutics, treatment options are limited, and clinical prognosis is poor. To establish a novel platform and methodology to better characterize ALL subtypes and identify their pharmacologic vulnerabilities, we performed thermal proteome profiling of 20 childhood ALL cell lines.