AUTHOR=Andrade Francianne G. , Feliciano Suellen V. M. , Sardou-Cezar Ingrid , Brisson Gisele D. , Santos-Bueno Filipe V. dos , Vianna Danielle T. , Marques Luísa V. C. , Terra-Granado Eugênia , Zalcberg Ilana , Santos Marceli de O. , Costa Juliana T. , Noronha Elda P. , Thuler Luiz C. S. , Wiemels Joseph L. , Pombo-de-Oliveira Maria S. ,  The Brazilian Collaborative Study Group of Acute Leukemia , Alves Sarkis Renata , de Souza Barros Pereira Renata , Basegio Rosania Maria , de Brito Patrícia Carneiro , Córdoba José Carlos , Costa Imaruí , Fialho Eloisa Cartaxo Eloy , Fonseca Teresa Cristina Cardoso , Magalhães Isis Maria Quezado , da Luz Mamede Glaceanne Torres , Manzo Eda , Marques Rebeca Ferreira , Neves Gustavo Ribeiro , Nobrega Andrea Gadelha , Oliveira Claudia Teresa , de Paula Guedes Oliveira Renato , Epelman Sidnei , da Silva Ana Maria Marinho , Nunes Silva Luciana , dos Santos Souza Marcelo , de Souza Regiana Quinto , Taniguchi Adriano Nori Rodrigues , Trujillo Luciana Garcia , Wanderley Alayde Vieira 

TITLE=Pediatric Acute Promyelocytic Leukemia: Epidemiology, Molecular Features, and Importance of GST-Theta 1 in Chemotherapy Response and Outcome

JOURNAL=Frontiers in Oncology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.642744

DOI=10.3389/fonc.2021.642744

ISSN=2234-943X

ABSTRACT=Previous studies have suggested a variation in the incidence of acute promyelocytic leukemia (APL) among geographic regions with relatively higher percentages in the Latin American population. We aimed to explore the population burden of pediatric APL, gathering the information from population-based cancer registry (PBCR) and the APL diagnosis obtained throughout incident cases from a hospital-based cohort. The homozygous deletion in glutathione S-transferases (GSTs) leads to the loss of enzyme detoxification activity, possibly affecting treatment response. Mutations in the RAS pathway genes are also a key component of the disease both in pathogenesis and outcomes. We have assessed mutations in the RAS-MAP kinase pathway (FLT3, PTPN11, K-/NRAS) and GST variant predisposition risk in the outcome. Thirty-five APL cases (4.3%) were registered in the PBCR out of 805 AML cases in children and adolescents. The age-adjusted incidence rate was 0.03 per 100,000 person-years. One-hundred sixty-three APL patients were studied out of 931 AML cases (17.5%) from a hospital-based cohort. Mutations in FLT3, KRAS, and NRAS accounted for 52.1% of cases. Patients with APL presented a 5-year probability of overall survival of 67.3±5.8%. GSTT1 null genotype conferred adverse prognosis, with an estimated hazard ratio of 2.8, 95% confidence interval 1.2-6.9. We speculate that the GSTT1 polymorphism associated with therapeutic and would allow better overall survival of APL patients with GSTT1 null genotype.”.