BCR-ABL1 tyrosine kinase sustained MECOM expression in chronic myeloid leukaemia

Swagata Roy, Heather G. Jørgensen, Poornima Roy, Mohamed Abed El Baky, Junia V. Melo, Gordon Strathdee, Tessa L. Holyoake, Christopher Bartholomew

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)446-56
Number of pages11
JournalBritish Journal of Haematology
Volume157
Issue number4
Early online date29 Feb 2012
DOIs
Publication statusPublished - May 2012

Keywords

  • oncogene expression
  • leukaemia
  • cell lines
  • cell biology

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