Dysregulated transcriptional networks in KMT2A- and MLLT10 -rearranged T-ALL

Biomarker Research
Huining KangKsenia Matlawska-Wasowska

Abstract

For children and young adults with T-lineage acute lymphoblastic leukemia (T-ALL), event free survival following relapse is < 10%. We recently showed that rearrangements of the mixed lineage leukemia gene (KMT2A-R) are associated with induction failure and an inferior survival in T-ALL. Because there are currently no molecular features that inform treatment strategies in T-ALL, we hypothesized that transcriptional alterations related to KMT2A-R and MLLT10-R T-ALL could identify biologically relevant genes and signaling pathways for the development of targeted therapies for these groups of patients. We analyzed microarray data from a retrospective cohort of 100 T-ALL patients to identify novel targets for KMT2A (n = 12) or MLLT10 (n = 9) chimeras. We identified 330 probe sets that could discriminate between these groups, including novel targets, like RUNX2, TCF4 or MYO6. The results were further validated in two independent data sets and the functional networks were analyzed to identify pathways that may be of pathogenic or therapeutic relevance.

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Citations

Jul 29, 2020·Genes, Chromosomes & Cancer·Michelle O ForgioneDeborah L White
Jan 21, 2021·International Journal of Molecular Sciences·Anna MroczekMonika Lejman
Feb 9, 2021·The Journal of Clinical Investigation·Filip MatthijssensKsenia Matlawska-Wasowska

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Methods Mentioned

BETA
ubiquitination

Software Mentioned

R
GSEA
Gene Set Enrichment Analysis ( GSEA )
limma

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