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


RESULTS
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 in vitro.


CONCLUSIONS
Our observations implicate hEag1 as novel target for diagnostic, prognostic and/or therapeutic approaches in AML.
Agarwal
Jasmin R
JR
Max-Planck-Institute of Experimental Medicine, Hermann-Rein-Str, 3, 37075 Göttingen, Germany.
Griesinger
Frank
F
Stühmer
Walter
W
Pardo
Luis A
LA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels