Gene expression profile at single cell level of Wilms tumors and normal kidney tissues from an infant with Denys-Drash syndrom
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE223373 | GEO | 2024/01/17
REPOSITORIES: GEO
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Project description:In this study we explored the genotype of Infant ALL to detect MLL-cooperating aberrations, hidden to conventional techniques. In order to limit further heterogeneity, we focused on patients carrying the t(4;11) translocation, the most frequent genetic abnormality in Infant ALL. Final aim was to get new insights into the leukemia pathogenesis of this rare and aggressive disease, as well as providing the basis for discovering new genes for targeted therapy.
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Project description:Extensive molecular and prognostic characterization of wild-type MLL infant ALL. Background: Approximately 20% of all infant ALL cases carry wild-type (or germline) MLL genes. To date, wild-type MLL infant ALL patients are generally regarded as young pediatric precursor B-ALL patients, but extensive characterization of this specific patient group largely remains unacknowledged. Methods: We here studied a relatively large cohort of 78 wild-type MLL infant ALL samples, using clinical parameters, array-comparative genomic hybridization analysis, gene expression profiling, multiplex ligation-dependent probe amplification, and conventional sequencing. Findings: Wild-type MLL infant ALL patients are generally characterized by a lower incidence of favourable prognostic factors than pediatric (non-infant) B-ALL patients, and patients at high risk of therapy failure typically display an immature pro-B immunophenotype or respond poorly to prednisone. Using gene expression profiling, we found MEIS1 expression to additionally be highly predictive for clinical outcome in wild-type MLL infant ALL with a favourable prognosis in the wild-type MLL infants with low MEIS1 expression (DFS 88%% versus 50%, p=0•01). Overall the incidence of DNA copy number variations and genetic abnormalities in genes involved in B-cell differentiation is lower in wild-type MLL infant ALL patients as compared with pediatric precursor B-ALL patients. Interpretation: Wild-type MLL infant ALL represents a highly heterogeneous patient group, which cannot be unified by one or a few known recurrent genomic aberrations. High-level MEIS1 expression and an immature pro-B immunophenotype in high-risk wild-type MLL infant ALL patients shows parallel with the unfavourable prognosis of MLL-rearranged infant ALL patients. In contrast, wild-type MLL infant ALL patients expressing lower levels of MEIS1 and displaying more differentiated (pre-B or common) phenotypes may well be more related to pediatric precursor B-ALL patients older than 1 year of age. We advocate that a treatment strategy in wild-type MLL infant ALL based on MEIS1 expression could be beneficial for improving survival. Gene expression profiling of wild-type MLL infant ALL. Additional wild-type MLL infant ALL patient samples (n=17) to the earlier samples published under GSE19475 (GSM485309 to GSM485322).
2014-10-01 | E-GEOD-58565 | biostudies-arrayexpress
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| PRJEB34323 | ENA