RAG1 co‐expression signature identifies ETV6‐RUNX1‐like B‐cell precursor acute lymphoblastic leukemia in children
Autor: | Linda Fogelstrand, Dongfeng Chen, Yanara Marincevic-Zuniga, Alessandro Camponeschi, Gudmar Lönnerholm, Jonas Abrahamsson, Jessica Nordlund, Inga-Lill Mårtensson |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Cancer Research Oncogene Proteins Fusion Chromosomal translocation BCP‐ALL Translocation Genetic Inhibitor of Apoptosis Proteins Fusion gene 0302 clinical medicine hemic and lymphatic diseases RUNX1‐ Child RC254-282 Original Research Cancer Biology B-Lymphocytes like Microfilament Proteins leukemia Neoplasms. Tumors. Oncology. Including cancer and carcinogens Nuclear Proteins hemic and immune systems Hematology Neoplasm Proteins DNA-Binding Proteins Leukemia medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Core Binding Factor Alpha 2 Subunit RAG1 ETV6‐RUNX1‐like RUNX1 ETV6‐ Biology Recombination-activating gene 03 medical and health sciences Chloride Channels Precursor B-Cell Lymphoblastic Leukemia-Lymphoma medicine Humans Radiology Nuclear Medicine and imaging Hematologi RNA Messenger Gene BCP‐ B cell Angiopoietin-Like Protein 2 Adaptor Proteins Signal Transducing Chromosome Aberrations Homeodomain Proteins Cancer och onkologi Proto-Oncogene Proteins c-ets Gene Expression Profiling Membrane Proteins medicine.disease Repressor Proteins ETV6 ETV6‐RUNX1 030104 developmental biology Genetic marker Cancer and Oncology Cancer research ALL Transcriptome |
Zdroj: | Cancer Medicine Cancer Medicine, Vol 10, Iss 12, Pp 3997-4003 (2021) |
ISSN: | 2045-7634 |
Popis: | 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. The recombination‐activating genes (RAG) may play a role in leukemogenesis. We determined, therefore, in around 1600 BCP‐ALL samples which subtypes express RAG and defined a set of co‐expressed genes, the RAG1‐signature, which was thereafter used to identify potential new subtypes. We demonstrate that the RAG1‐signature identifies the recently described ETV6‐RUNX1‐like BCP‐ALL. |
Databáze: | OpenAIRE |
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