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Mapping cell mutations that lead to leukemia

As we age, cells in the blood-forming system of our bodies begin to accumulate mutations. These mutations aren’t all dangerous, but researchers have found that around 10 per cent of people aged 65 and over have cells in this system with known cancer-causing mutations that increase their risk of developing leukemia.

Exactly how these mutations lead to leukemia – and why leukemia develops in some people with these mutations and not in others – remains unknown. Dr. David Knapp, director of the Cellular Engineering Research Unit at the Institute for Research in Immunology and Cancer (IRIC) at the Université de Montréal, will use a 2023 Terry Fox New Investigator Award to answer these very questions.

“The goal of this project is to map a number of key cancer-causing mutations, seeing how they affect the normal functioning of blood stem cells and how they affect their ability to replicate and pass on these mutations,” says Dr. Knapp. “By creating this map, we will have a better understanding of when – and how – to target these mutations in order to stop leukemia from forming.”

Dr. Knapp will receive $433,850 over three years to perform this study. He and his lab team will use state-of-the-art genome editing techniques to introduce these mutations into normal blood stem cells. They will then measure the ability of these cells to survive and grow and compare them to blood stem cells without these mutations. Finally, they will measure the molecular states of these cells to identify how these mutations alter the cell machinery to change their capabilities.

This information will give insight into how these mutations gain dominance and may enable better predictions of what cells will go on to cause cancer and how to target them before it happens.

“Over the next three years, we hope to have this system mapped out so we can show the impact that each mutation has on the outcome of a cell and understand what is happening to this cell before it becomes leukemia,” explains Dr. Knapp. “This map will create a blueprint to begin to pinpoint how and when we need to intervene to stop these cells from becoming leukemia down the line.”

As part of the award, Dr. Knapp will also receive mentorship from a team of TFRI-funded researchers in British Columbia led by Dr. Aly Karsan at BC Cancer. This team has decades of experience studying leukemia and will provide Dr. Knapp with a fountain of knowledge and experience to help advance his research.

“One of the things that is unique about this award is how it seeds these collaborations through mentorship,” says Dr. Knapp. “Science nowadays is not something that can be done in a silo, so the more that we can work together and collaborate, the faster we are going to move towards the long-term vision, which in our case is to find ways to treat leukemia earlier, before it’s too late.”