Egan 2024

Leukemia and Lymphoma Society of Canada: Pediatric Blood Cancer Innovation Grant

The LLSC Pediatric Blood Cancer Innovation Grant challenges the current pediatric blood cancer treatment paradigm to address gaps and improve outcomes.  Kindred Foundation is proud to partner with LLSC again in 2024 to co-fund an application focused on pediatric acute myeloid leukemia (pAML). 

Dr. Grace Egan | SickKids, Toronto

The role of XPO2 in leukemia development in childhood and adolescent AML

Acute myeloid leukemia (AML) is a difficult-to-treat leukemia that develops in children, teens, and adults and is associated with high relapse rates. Many of the chemotherapy medicines that are used in AML target both leukemia and healthy cells, resulting in many side effects for patients. New agents are needed that better target leukemia cells, while protecting normal non-cancerous cells.

The nucleus of a cell is where the cell gets the instructions on how to behave, grow and divide. Cancer develops because cells grow abnormally and do not respond to stop signals in the nucleus. If proteins move into or out of the nucleus at the wrong time, they can give faulty instructions to the cell that can contribute to cancer development. These proteins enter and exit the nucleus with the help of transporters, known as importins and exportins. Many of these importins and exportins have not been studied in leukemia.

We recently discovered that high levels of the exportin, XPO2, are associated with worse outcomes in childhood and adolescent AML. This study will identify the role of XPO2 in leukemia development in childhood and adolescent AML. We will determine if certain genetic subtypes of childhood and adolescent AML are more reliant on XPO2, and thus more likely to benefit from therapies that stop this exportin from working.

2025 UPDATE: Researchers studied a protein called XPO2 in childhood and young adult acute myeloid leukemia (AML) and found that it plays a critical role in helping leukemia cells survive and grow. When XPO2 was reduced in leukemia cells, the cancer cells grew more slowly, were less able to survive, and were less likely to take hold and spread in mouse models, leading to longer survival. Importantly, reducing XPO2 did not harm normal blood-forming stem cells, suggesting it may be a safer treatment target. XPO2 levels were especially high in aggressive forms of AML linked to very poor outcomes, including leukemias with NUP98 and NUP214 gene fusions. The study also discovered that XPO2 helps leukemia cells make proteins by supporting ribosome production, revealing a new biological weakness that could be targeted by future therapies.