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Blood, 15 January 2007, Vol. 109, No. 2, pp. 740-746. Prepublished online as a Blood First Edition Paper on September 12, 2006; DOI 10.1182/blood-2006-04-019588. This Article Full Text Full Text (PDF) Supplemental Table and Figure All Versions of this Article: blood-2006-04-019588v1 109/2/740    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Leung, J. Articles by Tse, E. W. C. Search for Related Content PubMed PubMed Citation Articles by Leung, J. Articles by Tse, E. W. C. Related Collections Gene Expression Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Relationship of expression of aquaglyceroporin 9 with arsenic uptake and sensitivity in leukemia cells Jordy Leung1, Annie Pang1, Wai-Hung Yuen2, Yok-Lam Kwong1,, and Eric W. C. Tse1, 1 Departments of Medicine and 2 Chemistry, University of Hong Kong, Queen Mary Hospital, Hong Kong, China Arsenic trioxide (As2O3) is highly efficacious in acute promyelocytic leukemia (APL). Aquaglyceroporin 9 (AQP9) is a transmembrane protein that may be involved in arsenic uptake. In 10 of 11 myeloid and lymphoid leukemia lines, quantitative polymerase chain reaction (Q-PCR) and Western blotting showed that AQP9 expression correlated positively with As2O3-induced cytotoxicity. As a proof-of-principle, transfection of EGFP-tagged AQP9 to the hepatoma line Hep3B, not expressing AQP9 and As2O3 insensitive, led to membrane AQP9 expression and increased As2O3-induced cytotoxicity. Similarly, the chronic myeloid leukemia line K562 expressed low levels of AQP9 and was As2O3 insensitive. The K562EGFP-AQP9 transfectant accumulated significantly higher levels of intracellular arsenic than control K562EGFP when incubated with As2O3, resulting in significantly increased As2O3-induced cytotoxicity. Pretreatment of the myeloid leukemia line HL-60 with all-trans retinoic acid (ATRA) up-regulated AQP9, leading to a significantly increased arsenic uptake and As2O3-induced cytotoxicity on incubation with As2O3, which might explain the synergism between ATRA and As2O3. Therefore, AQP9 controlled arsenic transport and might determine As2O3 sensitivity. Q-PCR showed that primary APL cells expressed AQP9 significantly (2-3 logs) higher than other acute myeloid leukemias (AMLs), which might explain their exquisite As2O3 sensitivity. However, APL and AML with maturation expressed comparable AQP9 levels, suggesting that AQP9 expression was related to granulocytic maturation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Wang, G.-B. Zhou, P. Liu, J.-H. Song, Y. Liang, X.-J. Yan, F. Xu, B.-S. Wang, J.-H. Mao, Z.-X. Shen, et al. Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia PNAS, March 25, 2008; 105(12): 4826 - 4831. [Abstract] [Full Text] [PDF] Z.-Y. Wang and Z. Chen Acute promyelocytic leukemia: from highly fatal to highly curable Blood, March 1, 2008; 111(5): 2505 - 2515. [Abstract] [Full Text] [PDF]

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