title: ETV6/RUNX1 transcript is a target of RNA-binding protein IGF2BP1 in t(12;21)(p13;q22)-positive acute lymphoblastic leukemia.
abstract: The oncofetal RNA-binding protein IGF2BP1 (IGF2 mRNA binding protein 1) is overexpressed in a subset of cancers and promotes cell cycle, migration and aggressive phenotype by regulating post-transcriptionally a number of key mRNAs (e. g, ACTB, CD44, CTNNB1, KRAS, MAPK4, MYC, PTEN and others). IGF2BP1 is also overexpressed in t(12;21)(p13;q22)-positive acute lymphoblastic leukemia (ALL), but the biological significance of this phenomenon has not been addressed so far. We have identified leukemia fusion gene ETV6/RUNX1 mRNA to be highly enriched in immunoprecipitated fraction of endogenous IGF2BP1 from a model cell line REH and t(12;21)(p13;q22)-positive ALL samples. Furthermore, downregulation of IGF2BP1 by two-fold has resulted in a corresponding decrease of ETV6/RUNX1 mRNA validating this transcript as a target of IGF2BP1 protein in t(12;21)(p13;q22)-positive ALL. These data infer that IGF2BP1 is a potent regulator of ETV6/RUNX1 mRNA stability and potentially link this evolutionary-highly conserved protein to cell transformation events in ETV6/RUNX1-mediated leukemogenesis of t(12;21)(p13;q22)-positive ALL.
authors: Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania; Department of Immunology, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania. Electronic address: mindaugas.stoskus@santa.lt.
authors: Mindaugas
authors: M
authors: Stoskus
authors: Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania.
authors: Goda
authors: G
authors: Vaitkeviciene
authors: Department of Immunology, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania; Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania.
authors: Audrone
authors: A
authors: Eidukaite
authors: Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania; Clinics of Internal, Family Medicine and Oncology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
authors: Laimonas
authors: L
authors: Griskevicius
mesh_terms: D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002881:Chromosomes, Human, Pair 12; D002891:Chromosomes, Human, Pair 21; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000378:metabolism; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics* / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein; C406144:IGF2BP1 protein, human; C493728:RUNX1 protein, human
keywords: ETV6/RUNX1; IGF2BP1; TEL-AML1; t(12;21)(p13;q22)