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RAG1 co-expression signature identifies ETV6-RUNX1-like B-cell precursor acute lymphoblastic leukemia in children.

ABSTRACT: B-cell precursor acute lymphoblastic leukemia (BCP-ALL) can be classified into subtypes according to the genetic aberrations they display. For instance, the translocation t(12;21)(p13;q22), representing the ETV6-RUNX1 fusion gene (ER), is present in a quarter of BCP-ALL cases. However, around 10% of the cases lack classifying chromosomal abnormalities (B-other). In pediatric ER BCP-ALL, rearrangement mediated by RAG (recombination-activating genes) has been proposed as the predominant driver of oncogenic rearrangement. Herein we analyzed almost 1600 pediatric BCP-ALL samples to determine which subtypes express RAG. We demonstrate that RAG1 mRNA levels are especially high in the ETV6-RUNX1 (ER) subtype and in a subset of B-other samples. We also define 31 genes that are co-expressed with RAG1 (RAG1-signature) in the ER subtype, a signature that also identifies this subset of B-other samples. Moreover, this subset also shares leukemia and pro-B gene expression signatures as well as high levels of the ETV6 target genes (BIRC7, WBP1L, CLIC5, ANGPTL2) with the ER subtype, indicating that these B-other cases are the recently identified ER-like subtype. We validated our results in a cohort where ER-like has been defined, which confirmed expression of the RAG1-signature in this recently described subtype. Taken together, our results demonstrate that the RAG1-signature identifies the ER-like subtype. As there are no definitive genetic markers to identify this novel subtype, the RAG1-signature represents a means to screen for this leukemia in children.

SUBMITTER: Chen D

PROVIDER: S-EPMC8209579 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Unique long non-coding RNA expression signature in ETV6/RUNX1-driven B-cell precursor acute lymphoblastic leukemia.

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| S-EPMC3804944 | biostudies-literature

Unique long non-coding RNA expression signature in ETV6/RUNX1-driven B-cell precursor acute lymphoblastic leukemia

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-09-26 | GSE79873 | GEO

The study of METTL3 and METTL14 expressions in childhood ETV6/RUNX1-positive acute lymphoblastic leukemia.

Project description:BACKGROUND:This study was aimed to explore the METTL3 and METTL14 expressions in children with ETV6/RUNX1(E/R)-positive acute lymphoblastic leukemia (ALL) and investigate the relation between the METTL3 and METTL14 expressions with clinical features. METHODS:Thirty-seven newly diagnosed E/R-positive ALL children and six controls were included in this study. Real-time quantitative polymerase chain reaction (RT-PCR) was used to detect the mRNA expression level of METTL3 and METTL14. RESULTS:Among the 37 cases, 51.35% (n = 19) were boys and 48.65% (n = 18) were girls and the median age was 4.72 (1.72-11.99) years. Among the six controls, 50% (n = 3) were boys and 50% (n = 3) were girls and the median age was 5.24 (1.53-13.17) years. The expression level of METTL3 and METTL14 in E/R-positive ALL patients were lower than in controls (p < .05). Although failed to achieve statistical significance, the expression level of METTL3 and METTL14 in relapse patients were lower than nonrelapse patients (p = .171, p = .150, respectively). CONCLUSION:The reduced levels of METTL3 and METTL14 suggest a possible role in the pathogenesis and course of E/R-positive ALL. METTL3 and METTL14 may become new prognostic factors, and rationalize specific treatment intensification in possible E/R-positive relapse patients.

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