The potassium channel Ether à go-go is a novel prognostic factor with functional relevance in acute myeloid leukemia

Molecular Cancer

Research

Frank Griesinger¹  Walter Stühmer²  Luis A Pardo²  Jasmin R Agarwal² 

[1] Department of Hematology and Oncology, University Medicine Göttingen, Robert-Koch Strasse 40, 37075, Göttingen, Germany;Max-Planck-Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075, Göttingen, Germany;

关键词: Acute Myeloid Leukemia;    Chronic Myeloid Leukemia;    K562 Cell;    Acute Myeloid Leukemia Patient;    Astemizole;   

DOI  :  10.1186/1476-4598-9-18

 received in 2009-10-09, accepted in 2010-01-27,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe voltage-gated potassium channel hEag1 (KV10.1) has been related to cancer biology. The physiological expression of the human channel is restricted to the brain but it is frequently and abundantly expressed in many solid tumors, thereby making it a promising target for a specific diagnosis and therapy. Because chronic lymphatic leukemia has been described not to express hEag1, it has been assumed that the channel is not expressed in hematopoietic neoplasms in general.ResultsHere we show that this assumption is not correct, because the channel is up-regulated in myelodysplastic syndromes, chronic myeloid leukemia and almost half of the tested acute myeloid leukemias in a subtype-dependent fashion. Most interestingly, channel expression strongly correlated with increasing age, higher relapse rates and a significantly shorter overall survival. Multivariate Cox regression analysis revealed hEag1 expression levels in AML as an independent predictive factor for reduced disease-free and overall survival; such an association had not been reported before. As a functional correlate, specific hEag1 blockade inhibited the proliferation and migration of several AML cell lines and primary cultured AML cells in vitro.ConclusionOur observations implicate hEag1 as novel target for diagnostic, prognostic and/or therapeutic approaches in AML.

【 授权许可】

Unknown   
© Agarwal et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.