title: Human AQP5 plays a role in the progression of chronic myelogenous leukemia (CML).
abstract: 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.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Young Kwang
authors.initials: YK
authors.lastname: Chae
authors.forename: Sung Koo
authors.initials: SK
authors.lastname: Kang
authors.forename: Myoung Sook
authors.initials: MS
authors.lastname: Kim
authors.forename: Janghee
authors.initials: J
authors.lastname: Woo
authors.forename: Juna
authors.initials: J
authors.lastname: Lee
authors.forename: Steven
authors.initials: S
authors.lastname: Chang
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Myungshin
authors.initials: M
authors.lastname: Kim
authors.forename: Seonyang
authors.initials: S
authors.lastname: Park
authors.forename: Inho
authors.initials: I
authors.lastname: Kim
authors.forename: Bhumsuk
authors.initials: B
authors.lastname: Keam
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Rhee
authors.forename: Nam Hee
authors.initials: NH
authors.lastname: Koo
authors.forename: Gyeongsin
authors.initials: G
authors.lastname: Park
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Se-Eun
authors.initials: SE
authors.lastname: Jang
authors.forename: Il-Young
authors.initials: IY
authors.lastname: Kweon
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
authors.forename: Chulso
authors.initials: C
authors.lastname: Moon
mesh_terms: 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
chemical_list: C496036:AQP5 protein, human; D051402:Aquaporin 5; D034741:RNA, Small Interfering