Accession PRJCA002270
Title Integrated Genomic Analyses Identify High-Risk Factors Associated with Poor Outcomes of T-ALL
Relevance Medical
Data types Exome
Transcriptome or Gene expression
Organisms Homo sapiens
Description T-ALL is an aggressive hematologic malignancy and adult T-ALLs are often associated with poor outcomes. Recent large-scale genomic landscape studies have identified frequently mutated genes and dysregulated pathways in major subtypes of T-ALLs1-3. However, few of these large-scale genomic analyses contain survival-related data, which makes molecular-based prognosis and designs of new targeted therapies difficult. In this study, we performed integrated genomic and transcriptomic analyses on samples from 137 pediatric and adult T-ALL patients, of which 90% have outcome information. Out of 54 recurrently mutated genes, we identified poor outcome-associated mutations in EZH2, ASXL1, KRAS, IDH2, JAK3, RB1, KMT2C, TCF7 gene (high-risk gene) and in the RAS pathway. The status of the high-risk gene and RAS pathway mutation groups were independent predictors than factors related with age and clinical features. By combining public datasets, we demonstrated that Asian and adult T-ALLs had higher rates of high-risk gene and Ras pathway mutations than that of Caucasian and pediatric T-ALLs. We also found that differentially expressed genes in early T progenitor ALL (ETP ALL) subtype were largely controlled by the transcription factor PU.1 and that the PU.1-TIM3-GAL-9 regulatory loop was essential for the formation and maintenance of ETP ALL.
Sample scope Monoisolate
Release date 2021-12-01
Publication
PubMed ID Article title Journal name DOI Year
35399540 Integrated genomic analyses identify high-risk factors and actionable targets in T-cell acute lymphoblastic leukemia Blood Science 10.1097/BS9.0000000000000102 2022
35831833 High expression of TMEM244 is associated with poor overall survival of patients with T-cell lymphoma Biomarker Research 10.1186/s40364-022-00395-z 2022
36056685 TNFAIP3 mutation is an independent poor overall survival factor for patients with T‐cell acute lymphoblastic leukemia Cancer Medicine 10.1002/cam4.5196 2023
Grants
Agency program Grant ID Grant title
No funding support
Submitter Hong     Wu  (gsmwhlab@pku.edu.cn)
Organization Peking University
Submission date 2020-02-25

Project Data

Resource name Description
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