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Relevant mouse model for human monocytic leukemia through Cre/lox-controlled myeloid-specific deletion of PTEN

Leukemia volume 24, pages 1077–1080 (2010)Cite this article

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Acute monoblastic and monocytic leukemia is a distinct subtype of acute myeloid leukemia (AML) (also known as AML-FAB subtype M5) and comprises ∼5 to 10% of all cases of AML. AML-M5 is currently treated with chemotherapy (such as anthracyclines) and/or with bone marrow transplantation. The development of more specific and effective therapies was hampered in part by the lack of proper animal models for this subtype of leukemia. Here, we report a mouse model for this entity. This is the first and the only relevant nonviral-based animal model for human monocytic leukemia.

One commonly used strategy for generating mouse solid tumor or leukemia models is to enhance the strength of tumor-promoting signals. One such signal is PtdIns(3,4,5)P3/Akt signaling pathway. PtdIns(3,4,5)P3 exerts its function by mediating protein translocation by binding to their pleckstrin homolog domains. PKB/Akt, a pleckstrin homolog domain containing serine/threonine protein kinase with oncogenic and anti-apoptotic activities, is one of the major downstream factors of PtdIns(3,4,5)P3. Hyperactivation of PtdIns(3,4,5)P3/Akt signaling pathway is frequently identified in a variety of cancers and is highly related to tumorigenesis. It has also been implicated in leukemia tumorigenesis. About 50–70% of AMLs display hyperactivation of this pathway.1 Accordingly, we examined whether monocytic leukemia can be induced by specifically enhancing PtdIns(3,4,5)P3 signaling in myeloid cells.

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Author notes

  1. H Yu, Y Li and C Gao: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Hospital Laboratories, UMass Memorial Medical Center, One Biotech Park, Worcester, MA, USA

    H Yu

  2. Department of Pathology, UMass Memorial Medical Center, One Biotech Park, Worcester, MA, USA

    H Yu

  3. Department of Pathology, Harvard Medical School, Children's Hospital Boston, Boston, MA, USA

    Y Li, C Gao, L Fabien, Y Jia, J Lu, L E Silberstein, L Chai & H R Luo

  4. Department of Lab Medicine, Children's Hospital Boston, Boston, MA, USA

    Y Li, C Gao, L Fabien, Y Jia, J Lu, L E Silberstein, L Chai & H R Luo

  5. Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

    C Gao, G S Pinkus & L Chai

  6. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA

    K Ye

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  1. H Yu
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  11. H R Luo
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Correspondence to H R Luo.

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The authors declare no conflict of interest.

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Supplementary Information accompanies the paper on the Leukemia website

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Yu, H., Li, Y., Gao, C. et al. Relevant mouse model for human monocytic leukemia through Cre/lox-controlled myeloid-specific deletion of PTEN. Leukemia 24, 1077–1080 (2010). https://doi.org/10.1038/leu.2010.34

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