Leveraging the ubiquitin proteasome system for targeted therapy in Acute Myeloid Leukemia

Acute Myeloid Leukemia (AML) is an aggressive type of blood cancer that develops rapidly, affecting both the blood and bone marrow. It is particularly dangerous, responsible for about one-third of all leukemia cases in adults, and, unfortunately, the chances of long-term survival are often poor. Therefore, there is an urgent need to find new and more effective ways to treat this deadly disease.

Our research group has uncovered an exciting clue in the fight against AML. We have identified a key protein, DCAF15, that AML cells rely on to grow and divide. DCAF15 helps these cancer cells to manage processes essential for their survival, making it a promising target for new therapies. In simpler terms, if we can block or remove DCAF15, we may be able to stop the cancer from growing.

The goal of our study is to understand exactly how DCAF15 works in both healthy and cancerous blood cells. This is crucial because we want to make sure that targeting this protein does not harm normal cells. Our approach includes testing the effects of removing or disabling DCAF15 in several different models, like human leukemia cells, lab mice that have been altered to replicate human AML, and special models created from cancer cells taken directly from patients.

One of the most exciting parts of our research involves using advanced technology called PROTACs (proteolysis-targeting chimeras). These are specially designed molecules that can find and destroy specific proteins inside cells. We are developing PROTACs that can target and eliminate DCAF15, acting like precision weapons against the cancer cells. If successful, these PROTACs could stop AML cells from growing while leaving healthy cells unharmed.

To carry out this research, we are using a variety of cutting-edge tools and methods. We will use CRISPR technology to make precise changes to genes and understand their roles. We will also use next-generation DNA sequencing to see how cells change when DCAF15 is removed or blocked, and we will work with chemists to create and test our PROTACs. By studying the impact of these new drugs in different models, we hope to lay the groundwork for a powerful and targeted therapy against AML.

In the end, our work could lead to a deeper understanding of how AML works and offer a new, targeted way to treat this devastating disease. We aim to create therapies that specifically attack cancer cells and give patients better outcomes with fewer side effects.