Molecular Characterization of Pediatric Acute Myeloid Leukemia: Results of a Multicentric Study in Brazil
| Autor: | Rosania Basegio, Virginia Maria Coser, Marcelo Santos Souza, Renata Silva de Carvalho Gurgel, José Carlos Córdoba, Gustavo Zamperlini, Tállita Meciany Farias Vieira, Eloisa Cartaxo Eloy Fialho, Isis Q. Magalhães, Renato Melaragno, Maria S. Pombo-de-Oliveira, Eugênia Terra-Granado, Denise Browsfield Silva, Alejandro Mauricio Arancibia, Elda Pereira Noronha, Maura Rosane Valério Ikoma, Luiz Claudio Santos Thuler, Ingrid Koster, Eny Guimarães Carvalho, Gisele Dallapicola Brisson, Patricia Carneiro de Brito, Suellen Valadares Moura, Filipe dos Santos Vicente Bueno, Claudia T. Oliveira, Á.S. Dias, Ilana Zalcberg Renault, Fernando Werneck, Francianne Gomes Andrade, Bruno Marcelo Rocha Freire, Ingrid Sardou Cezar, Terezinha de Jesus Marques Salles, Adriana Vanessa Santini Deyl, Ana Maria Marinho, Gustavo Ribeiro Neves, Ana Paula Ferreira Freund Winn, Imaruí Costa |
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| Rok vydání: | 2016 |
| Předmět: |
Male
Acute promyelocytic leukemia Oncology Down syndrome medicine.medical_specialty Oncogene Proteins Fusion Gene mutation medicine.disease_cause 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine hemic and lymphatic diseases Internal medicine Humans Medicine Child neoplasms Genetic Association Studies biology business.industry Gene Expression Profiling Childhood Acute Myeloid Leukemia General Medicine Prognosis medicine.disease Survival Analysis PTPN11 Leukemia Myeloid Acute KMT2A RUNX1 chemistry Child Preschool 030220 oncology & carcinogenesis Mutation Immunology biology.protein Female KRAS business Brazil 030215 immunology |
| Zdroj: | Archives of Medical Research. 47:656-667 |
| ISSN: | 0188-4409 |
| Popis: | Background and Aims The biological characterization of childhood acute myeloid leukemia (c-AML) is an important outcome predictor. In Brazil, very little is known about the frequency of AML subgroups, although c-AML accounts for about 18% of leukemias. We carried out this study to investigate the contribution of type I and II gene mutations in the probability of overall survival (pOS) of c-AML in Brazil. Methods Seven hundred and three de novo pediatric AML cases (2000–2015) were assessed throughout a multicentric network study. Mutations in hotspot regions of FLT3 , NRAS , KRAS , PTPN11 , and c- KIT genes were analyzed as well as fusion genes ( RUNX1 - RUNX1T1 , MLL / KMT2A -r, CBFβ - MYH11 , and PML - RARα ) associated with AML. Patients were treated out of the clinical trial although following the BFM-AML2004 protocol. Acute promyelocytic leukemia (APL) was treated differently. AML with Down syndrome was excluded. Results There were significant differences in gene mutations among age ranges (≤2 years-old; >2–10 years old and ≥11 years old) and the nonrandom association between type I/II mutations. Lower white blood cell count (≤50 × 10 9 /L) was associated with RUNX1 - RUNX1T1 , whereas higher WBC with CBFβ-MYH11 ( p p = 0.03). pOS differences were observed between Brazilian regions. The South-Southeast regions had a better 5-year pOS, whereas the Midwest region presented the poorest pOS (23.7 ± 4.9%). PTPN11 mutations conferred an adverse prognosis as an independent prognostic factor. Conclusions Identification of genetic subgroups contributes to the molecular epidemiology and biology of AML worldwide, reflecting the profile of pediatric AML cases in Brazil. |
| Databáze: | OpenAIRE |
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