Human AQP5 plays a role in the progression of Chronic Myelogenous Leukemia (CML)

Young Kwang Chae, Sung Koo Kang, Myoung Sook Kim, Janghee Woo, Juna Lee, Steven Chang, Dong Wook Kim, Myungshin Kim, Seonyang Park, Inho Kim, Bhumsuk Keam, Jiyoung Rhee, Nam Hee Koo, Gyeongsin Park, Soo Hyun Kim, Se Eun Jang, Il Young Kweon, David Sidransky, Chulso Moon

Research output: Contribution to journalArticle

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 (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.

Original languageEnglish (US)
Article numbere2594
JournalPloS one
Volume3
Issue number7
DOIs
StatePublished - Jul 9 2008

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Chae, Y. K., Kang, S. K., Kim, M. S., Woo, J., Lee, J., Chang, S., Kim, D. W., Kim, M., Park, S., Kim, I., Keam, B., Rhee, J., Koo, N. H., Park, G., Kim, S. H., Jang, S. E., Kweon, I. Y., Sidransky, D., & Moon, C. (2008). Human AQP5 plays a role in the progression of Chronic Myelogenous Leukemia (CML). PloS one, 3(7), [e2594]. https://doi.org/10.1371/journal.pone.0002594