Acute Myeloid Leukemia (AML) is a challenging cancer of the blood. Venetoclax is a common treatment in AML that improved outcomes. The prognosis for patients after relapse is extremely poor, with survival typically limited to a few months. Our goal is to uncover why this happens and to develop new strategies to prevent therapy resistance and relapse, thereby enhancing patient survival. To do this, we need to understand how AML cells reshape its environment. Our preliminary work shows a strong link between a specific inflammation signal, known as interferon gamma, and resistance to venetoclax. The same signal also turns AML cells into more primitive cells that are known for resisting treatmen...

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Acute Myeloid Leukemia (AML) is a challenging cancer of the blood. Venetoclax is a common treatment in AML that improved outcomes. The prognosis for patients after relapse is extremely poor, with survival typically limited to a few months. Our goal is to uncover why this happens and to develop new strategies to prevent therapy resistance and relapse, thereby enhancing patient survival. To do this, we need to understand how AML cells reshape its environment. Our preliminary work shows a strong link between a specific inflammation signal, known as interferon gamma, and resistance to venetoclax. The same signal also turns AML cells into more primitive cells that are known for resisting treatment. We also identified a protein called IFITM3, which is connected to interferon gamma, as a major player in AML's resistance to treatment. This suggests that the cancer cells might be tricking the immune system by exploiting interferon gamma to grow and hide. Based on these findings, we have devised a three-step strategy. Initially, we will utilize advanced imaging techniques to investigate the alterations occurring in the AML environment when treated with venetoclax. Next, we will investigate the impact of inflammation signals on drug resistance by simulating these interactions. Finally, we will examine the role of interferon gamma and IFITM3 in generating drug-resistant AML cells using preclinical mouse models that closely resemble the behavior of the disease in humans. Our study takes unique and innovative approaches to address the issue of venetoclax resistance by reevaluating the role of interferon gamma, which is generally thought to help the immune system fight cancer. However, our findings suggest it might promote the cancer cells to resist treatment. If our work is successful, it could lead to new treatment strategies for AML by targeting interferon gamma, ultimately helping patients live longer.

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