Researchers at Emory University, Georgia Tech, and Children's Healthcare of Atlanta developed GradientScreen, a lab-on-a-chip microfluidic assay that predicts treatment response in pediatric acute lymphoblastic leukemia at diagnosis. Published in Nature Biomedical Engineering, a retrospective study of 17 patient samples demonstrated that the technology correlates with residual disease and relapse outcomes by evaluating three-drug combination responses from a single blood or bone marrow sample.
Validation and predictive performance
- ▪A study published in Nature Biomedical Engineering demonstrated that GradientScreen can screen drug combinations directly on live cancer cells.
- ▪GradientScreen predicts pediatric acute lymphoblastic leukemia treatment responses at the time of diagnosis before standard chemotherapy administration.
- ▪A retrospective study of 17 patient samples from The Aflac Cancer and Blood Disorders Center showed GradientScreen results correlated with residual disease and relapse outcomes.
GradientScreen development and mechanics
- ▪GradientScreen evaluates combination ratios within a three-drug regimen in a single experiment using a single blood or bone marrow sample.
- ▪GradientScreen measures leukemia cell responses to drug combinations to identify effective drug pairs, dose ratios, and response patterns.
- ▪Kendall Williams, PhD, Dan Zhang, PhD, and researchers at Emory University, Children's Healthcare of Atlanta, and Georgia Tech developed GradientScreen, a lab-on-a-chip microfluidic assay measuring cell survival against three-drug combinations.
Personalizing leukemia treatment
- ▪Current acute lymphoblastic leukemia treatment strategies incorporate subtype and risk classification for personalization, but most patients still receive similar treatment regimens.
- ▪GradientScreen complements genomic sequencing data by directly measuring drug sensitivity in patients who share identical genetic mutations but display different drug responses.
Acute lymphoblastic leukemia impact and relapse
- ▪Acute lymphoblastic leukemia accounts for 75% of all pediatric leukemia diagnoses and prevents the body from producing mature, infection-fighting white blood cells.
- ▪Approximately 15% of pediatric patients and 50% of adult patients with acute lymphoblastic leukemia experience disease relapse or refractory disease.
- ▪In the U.S., over 120,000 people live with acute lymphoblastic leukemia (ALL), with 6,000 new cases diagnosed yearly, including more than 3,500 in children.
Future expansion and study funding
- ▪Researchers plan to expand GradientScreen testing to acute myeloid leukemia, adult patients, and the Emory Lab for Innovative Assay Development.
- ▪The GradientScreen study received funding support from National Science Foundation GRFP award 1937971 and National Institutes of Health NHLBI grant R35HL145000.
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