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
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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