Trial reportJournal of the National Cancer Institute2021
Association of GATA3 Polymorphisms With Minimal Residual Disease and Relapse Risk in Childhood Acute Lymphoblastic Leukemia.
Trial report in Journal of the National Cancer Institute, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Review
- Article
- Review
- Concepts in B cell acute lymphoblastic leukemia pathogenesis.Journal of leukocyte biology · 2024Review
- Genes of Predisposition to Childhood Beta-Cell Acute Lymphoblastic Leukemia in the Kazakh Population.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- Germline genetic variants and pediatric rhabdomyosarcoma outcomes: a report from the Children's Oncology Group.Journal of the National Cancer Institute · 2023Article
- The genetic risk of acute lymphoblastic leukemia and its implications for children of Latin American origin.Frontiers in oncology · 2023Review
- Impact of T-cell immunity on chemotherapy response in childhood acute lymphoblastic leukemia.Blood · 2022Article
- Identification of Genomic Variants Associated with the Risk of Acute Lymphoblastic Leukemia in Native Americans from Brazilian Amazonia.Journal of personalized medicine · 2022Article
- Recent Advances in Pediatric Cancer Research.Cancer research · 2021Review
- Inherited GATA3 variant associated with positive minimal residual disease in childhood B-cell acute lymphoblastic leukemia via asparaginase resistance.Clinical and translational medicine · 2021Article
- Pediatric Rhabdomyosarcoma: Epidemiology and Genetic Susceptibility.Journal of clinical medicine · 2021Review
- Comprehensive Overview of Gene Rearrangements in Childhood T-Cell Acute Lymphoblastic Leukaemia.International journal of molecular sciences · 2021Review
- Article
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26 authors at 13 institutions in 3 countries.
Funding
Abstract
backgroundMinimal residual disease (MRD) after induction therapy is one of the strongest prognostic factors in childhood acute lymphoblastic leukemia (ALL), and MRD-directed treatment intensification improves survival. Little is known about the effects of inherited genetic variants on interpatient variability in MRD.
methodsA genome-wide association study was performed on 2597 children on the Children's Oncology Group AALL0232 trial for high-risk B-cell ALL. Association between genotype and end-of-induction MRD levels was evaluated for 863 370 single nucleotide polymorphisms (SNPs), adjusting for genetic ancestry and treatment strata. Top variants were further evaluated in a validation cohort of 491 patients from the Children's Oncology Group P9905 and 6 ALL trials. The independent prognostic value of single nucleotide polymorphisms was determined in multivariable analyses. All statistical tests were 2-sided.
resultsIn the discovery genome-wide association study, we identified a genome-wide significant association at the GATA3 locus (rs3824662, odds ratio [OR] = 1.58, 95% confidence interval [CI] = 1.35 to 1.84; P = 1.15 × 10-8 as a dichotomous variable). This association was replicated in the validation cohort (P = .003, MRD as a dichotomous variable). The rs3824662 risk allele independently predicted ALL relapse after adjusting for age, white blood cell count, and leukemia DNA index (P = .04 and .007 in the discovery and validation cohort, respectively) and remained prognostic when the analyses were restricted to MRD-negative patients (P = .04 and .03 for the discovery and validation cohorts, respectively).
conclusionInherited GATA3 variant rs3824662 strongly influences ALL response to remission induction therapy and is associated with relapse. This work highlights the potential utility of germline variants in upfront risk stratification in ALL.
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