title: Defining the significance of IGF2BP1 overexpression in t(12;21)(p13;q22)-positive leukemia REH cells.
abstract: The IGF2 mRNA binding protein 1 (IGF2BP1) belongs to a family of regulatory RNA-binding proteins and controls stability, transport or translation of its target transcripts. Re-expression of IGF2BP1 is frequently found in different tumors and has been associated with aggressive disease phenotypes. IGF2BP1 has also been identified to be exclusively specific for t(12;21)(p13;q22)-positive acute lymphoblastic leukemia (ALL) but biological significance of IGF2BP1 overexpression has not been investigated to date. We have recently reported that ETV6/RUNX1 transcript is a target of RNA-binding protein IGF2BP1 in t(12;21)(p13;q22)-positive ALL suggesting a direct role of IGF2BP1 in ETV6/RUNX1-mediated leukemogenesis. To address this question we have employed stable clones of REH cells - a model cell line of t(12;21)(p13;q22)-positive ALL - with downregulated IGF2BP1 expression. Here we show that downregulation of IGF2BP1 impairs proliferation by attenuating cell cycle progression and increasing the rate of spontaneous cell death. We also provide evidence that downregulation of IGF2BP1 induce reduction of STAT3 mRNA levels and augments sensitivity to STAT3 selective inhibitor S3I-201. These data imply that IGF2BP1 indirectly potentiates ETV6/RUNX1-RAC1-STAT3 signaling axis by sustaining appropriate ETV6/RUNX1 and STAT3 transcript levels in REH cells. Further studies are warranted to specify the role of IGF2BP1 in t(12;21)(p13;q22)-positive ALL.
authors.affiliation: Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santariskiu Klinikos, Santariskiu 2, Vilnius 08661, Lithuania; Department of Immunology, State Research Institute Centre for Innovative Medicine, Santariskiu 5, Vilnius 08406, Lithuania. Electronic address: mindaugas.stoskus@santa.lt.
authors.forename: Mindaugas
authors.initials: M
authors.lastname: Stoskus
authors.affiliation: Department of Immunology, State Research Institute Centre for Innovative Medicine, Santariskiu 5, Vilnius 08406, Lithuania; Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos, Santariskiu 7, Vilnius 08406, Lithuania. Electronic address: audrone.eidukaite@vuvl.lt.
authors.forename: Audrone
authors.initials: A
authors.lastname: Eidukaite
authors.affiliation: Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santariskiu Klinikos, Santariskiu 2, Vilnius 08661, Lithuania; Clinics of Internal, Family Medicine and Oncology, Faculty of Medicine, Vilnius University, M.K. Ciurlionio 21, Vilnius 03101, Lithuania. Electronic address: laimonas.griskevicius@santa.lt.
authors.forename: Laimonas
authors.initials: L
authors.lastname: Griskevicius
mesh_terms: D002453:Cell Cycle; D016923:Cell Death; D049109:Cell Proliferation; D002881:Chromosomes, Human, Pair 12; D002891:Chromosomes, Human, Pair 21; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D050796:STAT3 Transcription Factor; C406144:IGF2BP1 protein, human; C494086:STAT3 protein, human; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein
keywords: ETV6/RUNX1; IGF2BP1; S3I-201; STAT3; TEL-AML1; t(12;21)(p13;q22)