The role of PDE4B in Racial Disparities in Outcome of Childhood Acute Lymphoblastic Leukemia

Cure rates of childhood acute lymphoblastic leukemia (ALL) have improved dramatically in the past decades. However, in 15-20% of children with ALL, the leukemia comes back after therapy and most children who relapse eventually succumb to the disease. Relapsed ALL is in fact one of the leading cause of death in children with cancer. Most importantly, ALL relapse is significantly more frequent in Hispanic children compared to Caucasians, and the underlying causes are largely unknown. In particular, it is unclear whether and how genetic make-up of the Hispanic children contributes to the racial disparities in leukemia survival. From genomic studies of over 2,500 children with ALL, Dr. Jun Yang from St. Jude Children's Research Hospital presents extensive evidence strongly indicating that certain genetic factors in a phosphodiesterase gene are unique in the Hispanic population and explain the higher risk of leukemia relapse in this ethnic group. In this application, Dr. Yang proposes to follow up on these exciting findings and perform in-depth investigation to identify the exact genetic variant form of phosphodiesterase that is responsible for racial differences in leukemia treatment response. He also plans to examine the possibility of developing new therapeutic agents that may overcome the excessive drug resistance in the Hispanic children with ALL.