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The interferon pathway attenuates acute myeloid leukemia development

  • Author(s): Lewin, Benjamin L.
  • et al.
Abstract

The fusion protein AML1-ETO is generated from the translocation t(8;21)(q22;q22) and is identified in over 12% of normal acute myeloid leukemia cases. While AML1-ETO does not induce acute myeloid leukemia in the murine retroviral transduction model, a spliced isoform, AML1- ETO9a, is able to induce acute myeloid leukemia. One difference between AML1-ETO and AML1-ETO9a is the ability of AML1-ETO to induce an interferon response to a greater degree than AML1-ETO9a. Here I verify that interferons and interferon stimulated genes are transcribed to a greater degree in the presence of AE than AE9a in the U937T cell lines. I also show that AE expression and universal interferon treatment inhibit proliferation in the U937T cell line. Next I verify in mouse bone marrow cells that AE induces interferon stimulated genes more effectively than AE9a. In addition, the induction of interferon stimulated genes is greater in bone marrow cells of C57BL/ 6 wild type mice than interferon receptor knockout mice. I also show that both global interferon treatment and loss of interferon receptor lead to decreases in proliferation and self-renewal ability. Finally I show that lethally irradiated mice treated with AE9a transduced fetal liver cells from mice without interferon receptor experience enhanced acute myeloid leukemia development compared to mice receiving AE9a transduced fetal liver cells from wild type mice. I also show that similar spleen and liver mass, and leukocyte composition is observed in leukemic mice regardless of the genotype of the donor fetal liver cells

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