Bcr–Abl dependent post-transcriptional activation of NME2 expression is a specific and common feature of chronic myeloid leukemia

Abstract

We have previously identified NME2 (Nm23-H2) as a tumor antigen in a patient with chronic myeloid leukemia (CML). Here we investigated the association between NME2 and Bcr–Abl. NME2 protein was highly overexpressed in the cytoplasm of peripheral blood mononuclear cells from 29/30 patients with CML at diagnosis and 10/10 patients resistant to imatinib. Protein was overexpressed in the absence of increased levels of mRNA and was limited to Bcr–Abl + populations, being absent from Bcr–Abl − patient cells, normal donors and 14/15 acute myeloid leukemia (AML) samples. Furthermore, the Bcr–Abl dependent overexpression of NME2 protein was reversed specifically by tyrosine kinase inhibitor (TKI) treatment of Ba/F3 expressing wild-type and TKI-sensitive, but not TKI-resistant, mutants of Bcr–Abl. The post-transcriptional up-regulation of the tumor antigen NME2 is therefore a common and specific property of CML closely associated with Bcr–Abl activity.

Keywords::

• NME2
• Nm23-H2
• CML
• tumor antigen
• Bcr–Abl

Acknowledgements

The authors would like to thank J. Grosche and A. Loesche (Core Unit “Fluorescence Technologies,” IZKF Leipzig, Germany) for technical assistance in laser scanning microscopy and cell sorting. This work was financed in part by MedSys grant 0315452A (HaematoSys) from the Bundesministerium für Bildung und Forschung.

Potential conflict of interest

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