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- Title
BCR- ABL1 tyrosine kinase sustained MECOM expression in chronic myeloid leukaemia.
- Authors
Roy, Swagata; Jørgensen, Heather G.; Roy, Poornima; Abed El Baky, Mohamed; Melo, Junia V.; Strathdee, Gordon; Holyoake, Tessa L.; Bartholomew, Chris
- 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 m RNA 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 m RNA 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.
- Subjects
PROTEIN-tyrosine kinases; GENE expression; CELL proliferation; CELL lines; CELL culture
- Publication
British Journal of Haematology, 2012, Vol 157, Issue 4, p446
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/j.1365-2141.2012.09078.x