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BCR ‐ ABL 1 tyrosine kinase sustained MECOM expression in chronic myeloid leukaemia
Author(s) -
Roy Swagata,
Jørgensen Heather G.,
Roy Poornima,
Abed El Baky Mohamed,
Melo Junia V.,
Strathdee Gordon,
Holyoake Tessa L.,
Bartholomew Chris
Publication year - 2012
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2012.09078.x
Subject(s) - imatinib mesylate , k562 cells , cancer research , tyrosine kinase , progenitor cell , biology , cd34 , abl , myeloid leukemia , imatinib , myeloid , microbiology and biotechnology , stem cell , leukemia , immunology , signal transduction
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.