| 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 |
| Source: |
British Journal of Haematology ; volume 157, issue 4, page 446-456 ; ISSN 0007-1048 1365-2141 |
| Publisher Information: |
Wiley |
| Publication Year: |
2012 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
Summary 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 K 562 cells. We also show that both E and ME are expressed in CD 34 + 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 CD 34 + cells, K 562 and KY 01 cell lines whereas imatinib had no effect in non‐ CML BCR ‐ ABL 1 −ve CD 34 + cells. Together these results suggest that BCR ‐ ABL 1 tyrosine kinase catalytic activity regulates MECOM gene expression in CML ‐ CP progenitor cells and that the BCR ‐ ABL 1 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1111/j.1365-2141.2012.09078.x |
| Availability: |
https://doi.org/10.1111/j.1365-2141.2012.09078.x; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1365-2141.2012.09078.x; https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2141.2012.09078.x |
| Rights: |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
| Accession Number: |
edsbas.2F3E0DA7 |
| Database: |
BASE |