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

<p>Abstract</p> <p>Background</p> <p>The voltage-gated potassium channel hEag1 (K<sub>V</sub>10.1) 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...

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Main Authors: Stühmer Walter, Griesinger Frank, Agarwal Jasmin R, Pardo Luis A
Format: Article
Language:English
Published: BMC 2010-01-01
Series:Molecular Cancer
Online Access:http://www.molecular-cancer.com/content/9/1/18
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spelling doaj-24a5286df862409f9fbafecabbf27b142020-11-24T21:25:19ZengBMCMolecular Cancer1476-45982010-01-01911810.1186/1476-4598-9-18The potassium channel Ether à go-go is a novel prognostic factor with functional relevance in acute myeloid leukemiaStühmer WalterGriesinger FrankAgarwal Jasmin RPardo Luis A<p>Abstract</p> <p>Background</p> <p>The voltage-gated potassium channel hEag1 (K<sub>V</sub>10.1) 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.</p> <p>Results</p> <p>Here 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 <it>in vitro</it>.</p> <p>Conclusion</p> <p>Our observations implicate hEag1 as novel target for diagnostic, prognostic and/or therapeutic approaches in AML.</p> http://www.molecular-cancer.com/content/9/1/18
collection DOAJ
language English
format Article
sources DOAJ
author Stühmer Walter
Griesinger Frank
Agarwal Jasmin R
Pardo Luis A
spellingShingle Stühmer Walter
Griesinger Frank
Agarwal Jasmin R
Pardo Luis A
The potassium channel Ether à go-go is a novel prognostic factor with functional relevance in acute myeloid leukemia
Molecular Cancer
author_facet Stühmer Walter
Griesinger Frank
Agarwal Jasmin R
Pardo Luis A
author_sort Stühmer Walter
title The potassium channel Ether à go-go is a novel prognostic factor with functional relevance in acute myeloid leukemia
title_short The potassium channel Ether à go-go is a novel prognostic factor with functional relevance in acute myeloid leukemia
title_full The potassium channel Ether à go-go is a novel prognostic factor with functional relevance in acute myeloid leukemia
title_fullStr The potassium channel Ether à go-go is a novel prognostic factor with functional relevance in acute myeloid leukemia
title_full_unstemmed The potassium channel Ether à go-go is a novel prognostic factor with functional relevance in acute myeloid leukemia
title_sort potassium channel ether à go-go is a novel prognostic factor with functional relevance in acute myeloid leukemia
publisher BMC
series Molecular Cancer
issn 1476-4598
publishDate 2010-01-01
description <p>Abstract</p> <p>Background</p> <p>The voltage-gated potassium channel hEag1 (K<sub>V</sub>10.1) 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.</p> <p>Results</p> <p>Here 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 <it>in vitro</it>.</p> <p>Conclusion</p> <p>Our observations implicate hEag1 as novel target for diagnostic, prognostic and/or therapeutic approaches in AML.</p>
url http://www.molecular-cancer.com/content/9/1/18
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