Produção Nacional
Revisado por pares
Childhood Myeloid Neoplasms With PTPN11 Mutations in Brazil
2020; Elsevier BV; Volume: 20; Issue: 8 Linguagem: Inglês
10.1016/j.clml.2020.04.009
ISSN2152-2650
AutoresFilipe V. dos Santos-Bueno, Francianne Gomes Andrade, Ingrid Sardou-Cezar, Daniela P. Mendes-de-Almeida, Alython Araújo Chung-Filho, Gisele Dallapicola Brisson, Eugênia Terra‐Granado, Elda Pereira Noronha, Luiz Cláudio Santos Thuler, Maria S. Pombo‐de‐Oliveira, Marcelo dos Santos Souza, Eda Manzo, Carolina Iracema de Oliveira Rego Patricia Carneiro de Brito, José Carlos Córdoba, Regiana Quinto de Souza, Juliana Teixeira Costa, Ana Maria Marinho, Eloisa Cartaxo Eloy Fialho, Renato de Paula Guedes Oliveira, Gustavo Ribeiro Neves, Alayde Vieira Wanderley, Everaldo Ruiz, Imaruí Costa,
Tópico(s)Ubiquitin and proteasome pathways
ResumoRecently, Hamdly et al reported the high frequency of gene mutation for RAS pathways, driving attention to the concept of mutually exclusive gene mutations observed in a series of juvenile myelomonocytic leukemia (JMML). 1 Hamdy N. Bokhary H. Elsayed A. et al. RAS pathway mutation patterns in patients with juvenile myelomonocytic leukemia: a developing country single-center experience. Clin Lymphoma Myeloma Leuk. 2020; ([Epub ahead of print]) Abstract Full Text Full Text PDF Scopus (4) Google Scholar We have focused on the PTPN11 somatic mutations in the molecular characterization of patients with myeloid neoplasms (MN) because they are scarcely explored in the context of a predictive marker. PTPN11 mutations are associated with myeloproliferative disorders, JMML, and acute myeloid leukemia (AML). However, when used as a biomarker, PTPN11 mutations may help to distinguish the MN subtypes. The PTPN11 gene encodes a cytoplasmic protein tyrosine phosphatase 2 (SHP-2) that is an effector of the RAS/MAPK pathway. 2 Tartaglia M. Niemeyer C.M. Fragale A. et al. Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes, and acute myeloid leukemia. Nat Genet. 2003; 34: 148-150 Crossref PubMed Scopus (761) Google Scholar ,3 Matozaki T. Murata Y. Saito Y. Okazawa H. Ohnishi H. Protein tyrosine phosphatase SHP-2: a proto-oncogene product that promotes Ras activation. Cancer Sci. 2009; 100: 1786-1793 Crossref PubMed Scopus (144) Google Scholar Germline mutations are described in approximately 50% of individuals with Noonan syndrome (NS), a disorder associated with a predisposition for childhood hematologic malignancies and bleeding disorders. 4 Tartaglia M. Kalidas K. Shaw A. et al. PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity. Am J Hum Genet. 2002; 70: 1555-1563 Abstract Full Text Full Text PDF PubMed Scopus (544) Google Scholar Residues D61, A72, and E76 codified by exon 3 and S502 and G503 codified by exon 13 are the most affected regions. Mutations in exons 3 and 13 lead to constitutive activation of the pathway as a consequence of increasing the catalytic activity of SHP-2 by reducing or eliminating the interaction of the N-SH2 and PTP domains that maintain SHP-2 in its inactive state. 2 Tartaglia M. Niemeyer C.M. Fragale A. et al. Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes, and acute myeloid leukemia. Nat Genet. 2003; 34: 148-150 Crossref PubMed Scopus (761) Google Scholar Our study aimed to explore genetic mutations in the RAS/MAPK pathway, to identify mutations in children and adolescents with MN with an emphasis on PTPN11 as a predictive marker.
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