HERG K+ channel expression in CD34+/CD38-/CD123(high) cells and primary leukemia cells and analysis of its regulation in leukemia cells.
The human ether-a-go-go-related (herg) gene encoding K+ channels (HERG) belongs to an evolutionarily conserved multigene family of voltage activated K+ channels. The functional properties of HERG K+ channels are complex and their contribution to the repolarization of the cardiac action potential are well understood. Recent studies revealed that HERG K+ channels are preferentially expressed in different histogenesis of tumor cells. Leukemia is a cancer that originates in the bone marrow hematopoietic stem cells (HSCs). Leukemia stem cells (LSCs) are critical in the perpetuation of the disease. A better understanding of LSCs and molecular biology will allow the design of more effective therapies. We report in this study that herg was expressed in CD34+/CD38-/ CD123(high) LSCs but not expressed in normal bone marrow CD34+/CD38- HSCs. In addtion, herg is also expressed in leukemia cell lines K562 and HL-60 and almost all the primary leukemia cells whereas not in the normal bone marrow cells. In addition, the expression of herg mRNA was not associated with the clinical and cytogenetic feature of leukemia. Moreover, HERG K+ channels can regulate leukemia cells proliferation and cell cycle. These data provide evidence for the oncogenic potential of HERG K+ channels and it may be a novel, potential pharmacological target for leukemia therapy in the future.
Li
Huiyu
H
Center for Stem Cell Research and Application, Institute of Hematology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiegang Avenue, 430022, Wuhan, China.
Liu
Liqiong
L
Center for Stem Cell Research and Application, Institute of Hematology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiegang Avenue, 430022, Wuhan, China.
Guo
Linlin
L
Center for Stem Cell Research and Application, Institute of Hematology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiegang Avenue, 430022, Wuhan, China.
Zhang
Jiahua
J
Center for Stem Cell Research and Application, Institute of Hematology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiegang Avenue, 430022, Wuhan, China.
Du
Wen
W
Center for Stem Cell Research and Application, Institute of Hematology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiegang Avenue, 430022, Wuhan, China.
Li
Xiaoqing
X
Center for Stem Cell Research and Application, Institute of Hematology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiegang Avenue, 430022, Wuhan, China.
Liu
Wei
W
Center for Stem Cell Research and Application, Institute of Hematology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiegang Avenue, 430022, Wuhan, China.
Chen
Xiangjun
X
Center for Stem Cell Research and Application, Institute of Hematology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiegang Avenue, 430022, Wuhan, China.
Huang
Shiang
S
Center for Stem Cell Research and Application, Institute of Hematology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiegang Avenue, 430022, Wuhan, China. sa2huang@hotmail.com.
D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics; D006801:Humans; D053650:Interleukin-3 Receptor alpha Subunit / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D007938:Leukemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics
D018952:Antigens, CD34; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D053650:Interleukin-3 Receptor alpha Subunit; C000606913:KCNH2 protein, human; D012333:RNA, Messenger; D051997:ADP-ribosyl Cyclase 1