1. Early-age Acute Leukemia: Revisiting Two Decades of the Brazilian Collaborative Study Group
- Author
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Rosania Maria Baseggio, Sergio Koifman, Soraya Rouxinol, Renata Silva de Carvalho Gurgel, Jose Carlos Martins Cordoba, Lilian Maria Cristofani, Joaquim Caetano Aguirre, Francianne Gomes Andrade, Lilian Maria Burlachini, Maria Luiza Macedo Silva, Jozina Marian de Andrade Agareno, Nilma Pimentel de Brito, Gilberto Ramos, Imaruí Costa, Maurício de Souza Meire, Ana Freund Winn, Gustavo Ribeiro Neves, Mara Albonei Dudeque Pianovski, Paulo Ivo Cortez de Araujo, Meyriele Bacarini Machado, Maria Dolores Dorea, Denise Bousfield Da Silva, Atalla Mnayarji, Marcelo Gerardin Poirot Land, Flavia Nogueira Serafim Araujo, Fernando de Almeida Wernerck, Cyntia Curvello, Monica Lankszner, Renato de Paula Guedes Oliveira, Ana M. Marinho da Silva, Maria Lucia Marinho Lee, Bruno Marcelo Rocha Freire, Claudia Teresa Oliveira, Mariana Emerenciano, Patricia Carneiro de Brito, Wellington Mendes, Alexandre Apa, Silvia R. Brandalise, Teresa Cristina Cardoso, Vitoria Regia Pinheiro, Isis Q. Magalhães, Eny Guimarães Carvalho, Á.S. Dias, Terezinha J. Marques Salles, Andrea Gadelha Nóbrega, Alejandro Mauricio Arancibe, Maria S. Pombo-de-Oliveira, Marcelo dos Santos Souza, Eloisa Cartaxo Eloy Fialho, Renato Melaragno, and Elaine Sobral da Costa
- Subjects
Male ,medicine.medical_specialty ,Genotype ,Gene mutation ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Epidemiology ,Genetic predisposition ,medicine ,Humans ,Genetic Predisposition to Disease ,Risk factor ,Child ,Acute leukemia ,Infant ,Transplacental ,Myeloid leukemia ,Histone-Lysine N-Methyltransferase ,General Medicine ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,Leukemia, Myeloid, Acute ,Leukemia ,Maternal Exposure ,030220 oncology & carcinogenesis ,Mutation ,Immunology ,Female ,Brazil ,Myeloid-Lymphoid Leukemia Protein ,030215 immunology - Abstract
The understanding of leukemogenesis in early-age acute leukemia (EAL) has improved remarkably. Initiating somatic mutations detected in dried neonatal blood spots (DNBS) and in cord blood samples of affected children with leukemia have been proven to be acquired prenatally. However, to date, few epidemiological studies have been carried out exploring EAL that include infants and children 13–24 months of age at the diagnosis. Maternal exposure to transplacental DNA-damaging substances during pregnancy has been suggested to be a risk factor for EAL. Most cases of infants with acute lymphoblastic (i-ALL) or myeloid leukemia (i-AML) have KMT2A gene rearrangements ( KMT2A-r ), which disturb its essential role as an epigenetic regulator of hematopoiesis. Due to the short latency period for EAL and the fact that KMT2A-r resembles those found in secondary AML, exposure to topoisomerase II inhibitors has been associated with transplacental risk as proxi for causality. EAL studies have been conducted in Brazil for over two decades, combining observational epidemiology, leukemia biology, and clinical data. EAL was investigated considering (i) age strata (infants vs. 13–24 months-old); (ii) somatic mutations associated with i-ALL and i-AML; (iii) ethnic-geographic variations; (iv) contribution of maternal genotypes; and (v) time latency of exposures and mutations in DNBS. Interactions of acquired and constitutive gene mutations are challenging tools to test risk factor associations for EAL. In this review we summarize the EAL scenario (including B-cell precursor-ALL, T-ALL, and AML) results combining environmental and genetic susceptibility risk factors and we raise questions that should be considered for further action.
- Published
- 2016
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