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:In the present study, we found that circADD2 was down-regulated in ALL tissues and cell lines. Overexpression of circADD2 inhibited cell proliferation and promoted apoptosis both in vitro and in vivo. Additionally, we found that miR-149-5p may increase the expression of the target gene AKT2 through the mechanism of RNAa, and the level of AKT2 can be reversed by circADD2. Briefly, circADD2 could directly sponge miR-149-5p to downregulate AKT2 expression.
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:ETV6/RUNX1 E/R -positive acute lymphoblastic leukemia (ALL), as one of the most common childhood malignancies, its pathogenesis and mechanism remain to be elucidated comprehensively. Global gene expression profiling can provide insight into the underlying pathophysiology of disease processes. In this study we sought to gain further insight into the molecular mechanisms underlying E/R-positive ALL by examining transcriptional profiles of E/R-positive ALL patients. We investigated the Bone marrow transcriptional profiles of E/R-positive ALL patients. Bioinformatic and statistical methods, including differential expression analysis, lncRNA analysis, alternative splicing analysis and metabolic network analysis, were used to characterize the underlying molecular mechanisms for E/R-positive ALL.