Mécanismes des désordres cardiométaboliques affectant les survivants de la leucémie lymphoblastique aiguë: Rôle préventif et thérapeutique de la nutrition

 

Valérie Marcil

Centre de recherche du CHU Sainte-Justine

 

Domaine :  nutrition et métabolisme

Programme chercheurs-boursiers  - Junior 1

Concours 2017-2018

The survival rate of childhood acute lymphoblastic leukemia (ALL) has remarkably improved and is now exceeding 80%. Nevertheless, for many patients, the price for this success story of modern medicine is very elevated given the intriguing wide spectrum of long-term sequelae. Data from our laboratory indicate a high occurrence of cardiometabolic complications such as obesity, dyslipidemia, insulin resistance and hypertension. Despite the importance of this problem, little is known about the precise causes and specific mechanisms leading to these late complications. While it is well established in the general population that diet plays an important role in the development of cardiovascular diseases nutrition has been poorly studied in survivors of pediatric cancer. Thereby, the major goals of this research program are to elucidate the mechanisms triggering the long-term cardiometabolic aberrations and to study the impact of nutrition in their development.

We have recently discovered that, in many childhood ALL survivors, the composition of the cholesterol transporter high-density lipoprotein (HDL) is altered. This is observed in parallel with an increased state of inflammation and oxidative stress. Knowing that HDL is the most powerful independent negative predictor of cardiovascular events, we are planning, in survivors of childhood ALL, to: (1) evaluate the size, composition and functions of HDL particles in association with oxidative stress, inflammation and cardiometabolic complications in pediatric ALL survivors; (2) explore the mechanisms that could explain these HDL alterations by studying the intestinal flora and epigenetic processes and; (3) study the impact of a nutritional intervention in children undergoing chemotherapy.

Understanding the causes of these complications will enable the identification of novel targets for preventive, diagnostic and curative intervention in this high-risk population and will contribute to achieve the full potential of nutrition therapy during cancer treatment in children.