HERG potassium channels are constitutively expressed in primary human acute myeloid leukemias and regulate cell proliferation of normal and leukemic hemopoietic progenitors.
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-gò-gò-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, hergappears 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.
Department of Experimental Pathology and Oncology, University of Firenze, Firenze, Italy.
S
S
Pillozzi
M F
MF
Brizzi
M
M
Balzi
O
O
Crociani
A
A
Cherubini
L
L
Guasti
B
B
Bartolozzi
A
A
Becchetti
E
E
Wanke
P A
PA
Bernabei
M
M
Olivotto
L
L
Pegoraro
A
A
Arcangeli
D000208:Acute Disease; D018952:Antigens, CD34 / Q000378:metabolism; D001562:Benzimidazoles / Q000494:pharmacology; D027682:Cation Transport Proteins; D002455:Cell Division / Q000502:physiology*; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007951:Leukemia, Myeloid / Q000378:metabolism* / Q000473:pathology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D013424:Sulfanilamides / Q000494:pharmacology; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology; D000096926:Benzenesulfonamides
D018952:Antigens, CD34; D001562:Benzimidazoles; D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D013424:Sulfanilamides; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; C072312:ERG protein, human; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; C073190:WAY 123398; D000096926:Benzenesulfonamides