HERG potassium channels are constitutively expressed in primary human acute myeloid leukemias and regulate cell proliferation of normal and leukemic hemopoietic progenitors

被引:160
作者
Pillozzi, S
Brizzi, MF
Balzi, M
Crociani, O
Cherubini, A
Guasti, L
Bartolozzi, B
Becchetti, A
Wanke, E
Bernabei, PA
Olivotto, M
Pegoraro, L
Arcangeli, A
机构
[1] Univ Florence, Dept Expt Pathol & Oncol, I-50134 Florence, Italy
[2] Univ Florence, Dept Clin Physiopathol, I-50134 Florence, Italy
[3] Policlin Careggi, UO Hematol, Florence, Italy
[4] Univ Milano Bicocca, Dept Biosci & Biotechnol, Milan, Italy
[5] Univ Turin, Dept Internal Med, Turin, Italy
关键词
AML; hemopoietic progenitors; CD34(+); HERG; herg; HERG inhibitors;
D O I
10.1038/sj.leu.2402572
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
An important target in the understanding of the pathogenesis of acute myeloid leukemias (AML) relies on deciphering the molecular features of normal and leukemic hemopoietic progenitors. In particular, the analysis of the mechanisms involved in the regulation of cell proliferation is decisive for the establishment of new targeted therapies. To gain further insight into this topic we report herein a novel approach by analyzing the role of HERG K+ channels in the regulation of hemopoietic cell proliferation. These channels, encoded by the human ether-a-go-go-related gene (herg), belong to a family of K, channels, whose role in oncogenesis has been recently demonstrated. We report here that herg is switched off in normal peripheral blood mononuclear cells (PBMNC) as well as in circulating CD34(+) cells, however, it is rapidly turned on in the latter upon induction of the mitotic cycle. Moreover, herg appears to be constitutively activated in leukemic cell lines as well as in the majority of circulating blasts from primary AML. Evidence is also provided that HERG channel activity regulates cell proliferation in stimulated CD34(+) as well as in blast cells from AML patients. These results open new perspectives on the pathogenetic role of HERG K+ channels in leukemias.
引用
收藏
页码:1791 / 1798
页数:8
相关论文
共 61 条
[51]   Protection from cell death by mcl-1 is mediated by membrane hyperpolarization induced by K+ channel activation [J].
Wang, L ;
Zhou, P ;
Craig, RW ;
Lu, L .
JOURNAL OF MEMBRANE BIOLOGY, 1999, 172 (02) :113-120
[52]   Growth factor-mediated K+ channel activity associated with human myeloblastic ML-1 cell proliferation [J].
Wang, L ;
Xu, B ;
White, RE ;
Lu, L .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1997, 273 (05) :C1657-C1665
[53]  
Wang SY, 1998, J CELL PHYSIOL, V176, P456, DOI 10.1002/(SICI)1097-4652(199809)176:3<456::AID-JCP2>3.0.CO
[54]  
2-N
[55]   A FAMILY OF POTASSIUM CHANNEL GENES RELATED TO EAG IN DROSOPHILA AND MAMMALS [J].
WARMKE, JW ;
GANETZKY, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (08) :3438-3442
[56]  
WeberNordt RM, 1996, BLOOD, V88, P809
[57]   Potassium channels, proliferation and G1 progression [J].
Wonderlin, WF ;
Strobl, JS .
JOURNAL OF MEMBRANE BIOLOGY, 1996, 154 (02) :91-107
[58]   Induction of human myeloblastic ML-1 cell G(1) arrest by suppression of K+ channel activity [J].
Xu, B ;
Wilson, BA ;
Lu, L .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1996, 271 (06) :C2037-C2044
[59]   A requirement for K+-channel activity in growth factor-mediated extracellular signal-regulated kinase activation in human myeloblastic leukemia ML-1 cells [J].
Xu, DZ ;
Wang, L ;
Dai, W ;
Lu, L .
BLOOD, 1999, 94 (01) :139-145
[60]   Activity of voltage-gated K+ channels is associated with cell proliferaton and Ca2+ influx in carcinoma cells of colon cancer [J].
Yao, XQ ;
Kwan, HY .
LIFE SCIENCES, 1999, 65 (01) :55-62