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

Roy, S., Jorgensen, H.G. , Roy, P., Abed El Baky, M., Melo, J.V., Strathdee, G., Holyoake, T.L. and Bartholomew, C. (2012) BCR-ABL1 tyrosine kinase sustained MECOM expression in chronic myeloid leukaemia. British Journal of Haematology, 157(4), pp. 446-456. (doi: 10.1111/j.1365-2141.2012.09078.x)

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.

• Item Type: Articles
• Additional Information: The definitive version is available at www.blackwell-synergy.com
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Holyoake, Professor Tessa and Jorgensen, Dr Heather
• Authors: Roy, S., Jorgensen, H.G., Roy, P., Abed El Baky, M., Melo, J.V., Strathdee, G., Holyoake, T.L., and Bartholomew, C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: British Journal of Haematology
• Publisher: Blackwell
• ISSN: 0007-1048
• Published Online: 29 February 2012
• Copyright Holders: Copyright © 2012 Blackwell
• First Published: First published in British Journal of Haematology 157(4):446-456
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher