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Acute myeloid leukemia

The novel function of CD82 and its impact on BCL2L12 via AKT/STAT5 signal pathway in acute myelogenous leukemia cells

Leukemia volume 29, pages 2296–2306 (2015)Cite this article

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Abstract

The aim of this study was to explore the biological functions of a tetraspanin family protein CD82 expressed aberrantly in chemotherapy-resistant CD34+/CD38− acute myelogenous leukemia (AML) cells. Microarray analysis of patient-isolated CD34+/CD38− AML cells revealed that the levels of anti-apoptotic protein BCL2L12 were downregulated after CD82 depletion by specific short hairpin RNA (shRNA). Western blot analysis indicated that BCL2L12 was aberrantly expressed in patient-isolated AML cells and AML cell lines. Furthermore, CD82 blockade by a specific antibody downregulated BCL2L12 in parallel with dephosphorylation of signal transducer and activator of transcription 5 (STAT5) and AKT, whereas pharmacological inhibition of STAT5 and AKT activation decreased BCL2L12 expression in leukemia cells. In addition, shRNA-mediated downregulation of BCL2L12 increased the levels of cleaved caspase-3 and suppressed proliferation of leukemia cells, impairing their engraftment in immunodeficient mice. Taken together, our results indicate that CD82 regulated BCL2L12 expression via STAT5A and AKT signaling and stimulated proliferation and engrafting of leukemia cells, suggesting that CD82 and BCL2L12 may be promising therapeutic targets in AML.

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Acknowledgements

This work was supported in part by Takeda Science Foundation (to CN) and JSPS KAKENHI Grant Number 14446690 (to CN).

Author contributions

Takayuki Ikezoe contributed to the concept and design, interpreted and analyzed the data and wrote the article. Chie Nishioka performed all experiments and wrote the article. Atsuya Nobumoto and Masayuki Tsuda provided technical support. Akihito Yokoyama provided critical revision and intellectual content.

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Authors and Affiliations

  1. Department of Hematology and Respiratory Medicine, Kochi University, Nankoku, Japan

    C Nishioka, T Ikezoe, A Takeuchi & A Yokoyama

  2. The Facility for Animal Research, Kochi Medical School, Kochi University, Nankoku, Japan

    A Nobumoto & M Tsuda

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  1. C Nishioka
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Correspondence to T Ikezoe.

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Nishioka, C., Ikezoe, T., Takeuchi, A. et al. The novel function of CD82 and its impact on BCL2L12 via AKT/STAT5 signal pathway in acute myelogenous leukemia cells. Leukemia 29, 2296–2306 (2015). https://doi.org/10.1038/leu.2015.219

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