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Open Access Publications from the University of California

Loss of Usp18 Impairs the Propagation of Myeloid Leukemia Cells in Mouse Models

  • Author(s): Zhang, Yue
  • Advisor(s): Zhang, Dong-Er
  • et al.

Acute Myloid Leukemia (AML) is one of the most common leukemia in adults with poor five years survival even with modern chemotherapy treatment. New strategies need to be developed in order to enhance the survival of AML patients. Interferon-α (IFN-α), a type I IFN, is a known as an anti-tumor agent, which used to clinical treat AML because of its anti-proliferative effect and immune response. However, the clinical trials show divergent results because of the instability and delivery difficulty. USP18 is a negative regulator of Type I IFN signaling pathway. Knockout Usp18 can enhance and prolong the Type I IFN pathway.

Here, we use AE9a-included leukemia mouse models that reflect the genetics and pathology of human acute myeloid leukemia to study the effect of Usp18 loss in leukemia development and to discover possible new therapeutic targets for leukemia. Results show that deletion of Usp18 delayed leukemia propagation in both the AE9a-induced and MLL-AF9-induced leukemia models. Usp18-deletion-mediated inhibition of myeloid leukemia propagation is IFN response dependent. More important, Usp18 deletion can delay the myeloid leukemia remission after the chemotherapy. These data indicate that pharmacological inhibition of Usp18 may be benefit in AML treatment with interferon prescribed.

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