The Molecular & Genetic Oncology Group

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, accounting for 25% of all cancers diagnosed in children and adolescents aged 1-18 years. Advances in our understanding of disease pathobiology have led to risk-targeted treatment regimens and increased survival rates that now exceed an impressive 80%. However despite significant improvement in the overall cure rate for childhood leukemia, treatment is far from optimal such that relapsed ALL remains the leading cause of cancer-related mortality in children. In fact up to 1 in 5 children do not respond to current therapy, and suffer poor prognosis. And due to the high doses of toxic chemicals these little patients receive during a crucial developmental period of their life, they are particularly vulnerable to debilitating short- and long-term side effects caused by both their cancer and its treatment. Better understanding of the causes of ALL is crucial in order to optimize the treatment and disease outcomes for children diagnosed with leukemia, with the ultimate goal of improving diagnosis to eventually prevent this disease.

Since 1994, Daniel Sinnett’s molecular oncogenetics laboratory at the Sainte-Justine University Hospital Center (SJUHC), the largest mother-child hospital in Canada, has made significant contributions towards deciphering the genetic and molecular mechanisms underlying childhood leukemia. He characterized hemizygous deletion of the ETV6 gene in childhood ALL patients, but also present in a wide range of hematological malignancies. And his team is now carrying out integrated research (DNA, RNA and protein analyses) aimed at better understanding the role of ETV6 tumour-suppressor in the development of leukemia. He has also spearheaded pioneering work in pediatric oncogenetics, which lead to the identification of a number of genetic variants (polymorphisms) that influence susceptibility to childhood leukemia and treatment response. He is currently involved in two large-scale genomic initiatives that involve the use of cutting-edge next-generation sequencing technologies to interrogate the entire genomes, transcriptomes, epigenomes of hundreds of childhood leukemia patients. Through an integrative analytical approach, these projects aim to better understand the underlying mechanisms driving leukemia onset and to identify clinically relevant biomarkers associated with long-term treatment morbidities. It is our hope that our research will lead to the development of new strategies and clinical tools that will ultimately improve detection, diagnosis and treatment of childhood leukemia and provide a better outlook for the thousands of children diagnosed with ALL each year.