RAG1 co-expression signature identifies ETV6-RUNX1-like B-cell precursor acute lymphoblastic leukemia in children [Elektronisk resurs]
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Chen, Dongfeng (författare)
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Camponeschi, Alessandro (författare)
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Nordlund, Jessica (författare)
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Marincevic-Zuniga, Yanara (författare)
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Abrahamsson, Jonas (författare)
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Lönnerholm, Gudmar, 1941- (författare)
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Fogelstrand, Linda (författare)
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Mårtensson, Inga-Lill (författare)
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barnonkologisk forskning - särskilt fokus på komplikationer (medarbetare)
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Uppsala universitet Medicinska och farmaceutiska vetenskapsområdet (utgivare)
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Uppsala universitet Science for Life Laboratory, SciLifeLab (utgivare)
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Uppsala universitet Medicinska och farmaceutiska vetenskapsområdet (utgivare)
- Publicerad: WILEY, 2021
- Engelska.
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Ingår i: Cancer Medicine. - 2045-7634. ; 10:12, 3997-4003
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Sammanfattning
Ämnesord
Stäng
- 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.
Ämnesord
- Medical and Health Sciences (hsv)
- Clinical Medicine (hsv)
- Hematology (hsv)
- Medicin och hälsovetenskap (hsv)
- Klinisk medicin (hsv)
- Hematologi (hsv)
- Medical and Health Sciences (hsv)
- Clinical Medicine (hsv)
- Cancer and Oncology (hsv)
- Medicin och hälsovetenskap (hsv)
- Klinisk medicin (hsv)
- Cancer och onkologi (hsv)
Genre
- government publication (marcgt)
Indexterm och SAB-rubrik
- BCP‐
- ALL
- ETV6‐
- RUNX1
- RUNX1‐
- like
- leukemia
- RAG1
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Cancer Medicine