Project 467167

Acute lymphoblastic leukemia (ALL) is a serious public health problem in the pediatric population affecting 1 in 1,500 children worldwide, and contributes to 85% of deaths from childhood cancer. It is an aggressive fast-growing cancer of white blood cells that gets worse quickly if left untreated. Thromboembolism is a well-recognized complication and the second leading cause of death in childhood ALL. Leukemic children who developed blood clots had to withhold or delay cancer therapy, which explains their significantly worse overall survival rate, compared to patients without thromboembolism. Although modern treatment protocols can effectively eradicate the leukemia and the child are expected to live several decades, thromboembolism leads to significant long-term physical, psychosocial and financial burden. Mechanisms underlying the development of thrombosis in ALL are multi-factorial and not well-understood. The disease itself, along with treatment components and patient characteristics contribute to a prothrombotic state. Understanding the biology of the disease is crucial for defining optimal strategy for prevention and management of ALL-associated thrombosis. In this project, I will explore thrombosis in ALL based on the Virchows triad framework, which describes the three board categories of factors contributing to thrombosis: Endothelial dysfunction, Hypercoagulability and Hemodynamic changes. Briefly, a co-culture model between healthy endothelium and donor leukemic blasts will be employed to evaluate the cell-to-cell interactions and how a prothrombotic environment is being promoted. Overall, these new findings will aid in preventing thrombosis at the first place as well as highlighting potential therapeutic targets for thrombosis control in patients with ALL.