Research published by Zhang et al in the Journal of the National Cancer Institute showed that an inherited variation in the GATA3 gene strongly influences early response to chemotherapy and is linked to relapse in children with acute lymphoblastic leukemia (ALL).
Minimal residual disease (MRD) checks for the presence of minute numbers of cancer cells after induction therapy, the first stage of ALL treatment. MRD is one of the strongest predictors of relapse risk for young patients with ALL.
“We know there is substantial variability in the way patients respond to ALL therapy. Certain mutations in leukemia cells are associated with drug response, but they certainly do not explain the full spectrum of the observed variability. This is when we realize we need to look at inherited genetic variants as well,” said corresponding author Jun J. Yang, PhD, of St. Jude Children’s Research Hospital.
Study Findings
The team conducted a genome-wide association study on children in Children’s Oncology Group clinical trials for high-risk B-ALL. This cohort was large enough for the scientists to look for associations between the inherited genetics and end-of-induction MRD levels for 863,370 single-nucleotide polymorphisms.
Results of the study showed that an inherited GATA3 variant strongly influenced how patients responded to therapy. This variant is also associated with relapse. GATA3 is known by scientists to encode a crucial transcription factor for the development and differentiation of T cells.
“This variant isn’t completely new to us; we’ve previously found it to be associated with susceptibility to Philadelphia chromosome-like ALL, a rare but high-risk subtype,” explained Dr. Yang. “These new findings about the relationship between the GATA3 variant and MRD solidify the potential utility of inherited variants in how we assess newly diagnosed patients for risk-stratified therapy.”
Disclosure: The research was funded in part by grants from the National Institutes of Health, a St. Baldrick’s Foundation International Scholar award, a National Medical Research Council Singapore Research Training Fellowship, and ALSAC, the fundraising and awareness organization of St. Jude. For full disclosures of the study authors, visit academic.oup.com.
