Human AQP5 plays a role in the progression of chronic myelogenous leukemia (CML).
Aquaporins (AQPs) have previously been associated with increased expression in solid tumors. However, its expression in hematologic malignancies including CML has not been described yet. Here, we report the expression of AQP5 in CML cells by RT-PCR and immunohistochemistry. While normal bone marrow biopsy samples (n = 5) showed no expression of AQP5, 32% of CML patient samples (n = 41) demonstrated AQP5 expression. In addition, AQP5 expression level increased with the emergence of imatinib mesylate resistance in paired samples (p = 0.047). We have found that the overexpression of AQP5 in K562 cells resulted in increased cell proliferation. In addition, small interfering RNA (siRNA) targeting AQP5 reduced the cell proliferation rate in both K562 and LAMA84 CML cells. Moreover, by immunoblotting and flow cytometry, we show that phosphorylation of BCR-ABL1 is increased in AQP5-overexpressing CML cells and decreased in AQP5 siRNA-treated CML cells. Interestingly, caspase9 activity increased in AQP5 siRNA-treated cells. Finally, FISH showed no evidence of AQP5 gene amplification in CML from bone marrow. In summary, we report for the first time that AQP5 is overexpressed in CML cells and plays a role in promoting cell proliferation and inhibiting apoptosis. Furthermore, our findings may provide the basis for a novel CML therapy targeting AQP5.
Chae
Young Kwang
YK
Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
Kang
Sung Koo
SK
Kim
Myoung Sook
MS
Woo
Janghee
J
Lee
Juna
J
Chang
Steven
S
Kim
Dong-Wook
DW
Kim
Myungshin
M
Park
Seonyang
S
Kim
Inho
I
Keam
Bhumsuk
B
Rhee
Jiyoung
J
Koo
Nam Hee
NH
Park
Gyeongsin
G
Kim
Soo-Hyun
SH
Jang
Se-Eun
SE
Kweon
Il-Young
IY
Sidransky
David
D
Moon
Chulso
C
D017209:Apoptosis; D051402:Aquaporin 5 / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D007150:Immunohistochemistry; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
C496036:AQP5 protein, human; D051402:Aquaporin 5; D034741:RNA, Small Interfering