title: BCR-ABL1 tyrosine kinase sustained MECOM expression in chronic myeloid leukaemia.
abstract: MECOM oncogene expression correlates with chronic myeloid leukaemia (CML) progression. Here we show that the knockdown of MECOM (E) and MECOM (ME) isoforms reduces cell division at low cell density, inhibits colony-forming cells by 34% and moderately reduces BCR-ABL1 mRNA and protein expression but not tyrosine kinase catalytic activity in K562 cells. We also show that both E and ME are expressed in CD34(+)  selected cells of both CML chronic phase (CML-CP), and non-CML (normal) origin. Furthermore, MECOM mRNA and protein expression were repressed by imatinib mesylate treatment of CML-CP CD34(+)  cells, K562 and KY01 cell lines whereas imatinib had no effect in non-CML BCR-ABL1 -ve CD34(+)  cells. Together these results suggest that BCR-ABL1 tyrosine kinase catalytic activity regulates MECOM gene expression in CML-CP progenitor cells and that the BCR-ABL1 oncoprotein partially mediates its biological activity through MECOM. MECOM gene expression in CML-CP progenitor cells would provide an in vivo selective advantage, contributing to CML pathogenesis.
authors.affiliation: Department of Life Sciences, City Campus, Glasgow Caledonian University, Glasgow, UK.
authors.forename: Swagata
authors.initials: S
authors.lastname: Roy
authors.forename: Heather G
authors.initials: HG
authors.lastname: Jørgensen
authors.forename: Poornima
authors.initials: P
authors.lastname: Roy
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abed El Baky
authors.forename: Junia V
authors.initials: JV
authors.lastname: Melo
authors.forename: Gordon
authors.initials: G
authors.lastname: Strathdee
authors.forename: Tessa L
authors.initials: TL
authors.lastname: Holyoake
authors.forename: Chris
authors.initials: C
authors.lastname: Bartholomew
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D001549:Benzamides; D002460:Cell Line; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics*; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D023061:Gene Order; D020868:Gene Silencing; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000378:metabolism*; D000074008:MDS1 and EVI1 Complex Locus Protein; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011519:Proto-Oncogenes / Q000235:genetics*; D011743:Pyrimidines / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018952:Antigens, CD34; D000970:Antineoplastic Agents; D001549:Benzamides; D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D014157:Transcription Factors; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl