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=11

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=<p>Previous studies have suggested a variation in the incidence of acute promyelocytic leukemia (APL) among the geographic regions with relatively higher percentages in the Latin American population. We aimed to explore the population burden of pediatric APL, gathering information from the population-based cancer registry (PBCR) and the diagnosis of APL obtained through incident cases from a hospital-based cohort. The homozygous deletion in glutathione S-transferases (GSTs) leads to a loss of enzyme detoxification activity, possibly affecting the treatment response. Mutations in the <italic>RAS</italic> pathway genes are also considered to be a key component of the disease both in the pathogenesis and in the outcomes. We have assessed mutations in a RAS–MAP kinase pathway (<italic>FLT3, PTPN11</italic>, and <italic>K</italic>-/<italic>NRAS</italic>) and <italic>GST</italic> variant predisposition risk in the outcome. Out of the 805 children and adolescents with acute myeloid leukemia (AML) who are registered in the PBCR, 35 (4.3%) were APL cases. The age-adjusted incidence rate (AAIR) was 0.03 per 100,000 person-years. One-hundred and sixty-three patients with APL were studied out of 931 AML cases (17.5%) from a hospital-based cohort. Mutations in <italic>FLT3, KRAS</italic>, and <italic>NRAS</italic> accounted for 52.1% of the cases. Patients with APL presented a 5-year probability of the overall survival (OS) of 67.3 ± 5.8%. A <italic>GST-theta 1</italic> (<italic>GSTT1</italic>) null genotype conferred adverse prognosis, with an estimated hazard ratio of 2.8, 95% confidence interval (CI) 1.2–6.9. We speculate that the GSTT1 polymorphism is associated with therapeutics and would allow better OS of patients with APL with a GSTT1 null genotype.</p>