title: RUNX1T1/MTG8/ETO gene expression status in human t(8;21)(q22;q22)-positive acute myeloid leukemia cells.
abstract: The RUNX1-RUNX1T1 fusion gene, a product of the nonhomologous balanced translocation t(8;21)(q22;q22), is a complex genetic locus. We performed extensive bioinformatic analysis of transcription initiation as well as transcription termination sites in this locus and predicted a number of different RUNX1T1 transcripts. To confirm and quantify the RUNX1T1 gene expression, we analyzed samples from seven acute myeloid leukemia (AML) patients and from the Kasumi-1 cell line. We found variable activity of the four predicted RUNX1T1 promoters located downstream of the chromosome breakpoint. Nineteen alternative RUNX1T1 transcripts were identified by sequencing at least seventeen of which predictably can be translated into functional proteins. While the RUNX1T1 gene is not expressed in normal hematopoietic cells, it may participate in t(8;21)(q22;q22)-dependent leukemic transformation due to its multiple interactions in cell regulatory network particularly through synergistic or antagonistic effects in relation to activity of RUNX1-RUNX1T1 fusion gene.
authors: Laboratory of the Genetic Biotechnology, Department of Research, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus.
authors: Alexandr A
authors: AA
authors: Migas
authors: Laboratory of the Genetic Biotechnology, Department of Research, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus.
authors: Olga A
authors: OA
authors: Mishkova
authors: Department of Genetics, Faculty of Biology, Belarusian State University, Minsk, Belarus.
authors: Tatiana V
authors: TV
authors: Ramanouskaya
authors: Department of Genetics, Faculty of Biology, Belarusian State University, Minsk, Belarus.
authors: Ilya M
authors: IM
authors: Ilyushonak
authors: Laboratory of the Genetic Biotechnology, Department of Research, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus.
authors: Olga V
authors: OV
authors: Aleinikova
authors: Department of Genetics, Faculty of Biology, Belarusian State University, Minsk, Belarus. Electronic address: grinev_vv@bsu.by.
authors: Vasily V
authors: VV
authors: Grinev
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic; D053263:Gene Regulatory Networks; D057809:HEK293 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000075142:RUNX1 Translocation Partner 1 Protein; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D011518:Proto-Oncogene Proteins; D000075142:RUNX1 Translocation Partner 1 Protein; C082222:RUNX1T1 protein, human; D014157:Transcription Factors
keywords: Alternative initiation of transcription; Alternative splicing; Human RUNX1T1 gene; t(8;21)(q22;q22)-positive AML