title: Clinical and molecular epidemiology of neonatal leukemia in Brazil.
abstract: The clinical and molecular findings of 77 cases of neonatal leukemia (NL) and 380 of infant leukemia (IL) were selected to distinguish features between NL and IL. Somatic gene mutations associated with acute leukemia including FLT3, RAS and PTPN11 were revisited. There were 42 cases of congenital leukemia associated with Down syndrome (DS) and 39 of these cases presented features of acute myeloid leukemia (AML)-M7. Twenty-seven of the DS cases underwent spontaneous remission and were reclassified as a transient myeloproliferative disorder. GATA1 mutations were found in 70% of these cases. In non-DS, frequent abnormalities were MLL rearrangements, mainly MLL-AFF1 in acute lymphoblastic leukemia and MLL-MLLT3 in AML. The FLT3 mutation was not found, while RAS (n = 4) and PTPN11 (n = 2) mutations were identified and reported for the first time in NL. There was substantial evidence to support that somatic abnormalities occur in utero. Thus, congenital leukemia is a good model for understanding leukemogenesis.
authors.affiliation: Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Câncer , Rio de Janeiro , Brazil.
authors.forename: Suellen Valadares
authors.initials: SV
authors.lastname: Moura
authors.forename: Francianne
authors.initials: F
authors.lastname: Andrade
authors.forename: Isis Q
authors.initials: IQ
authors.lastname: Magalhães
authors.forename: Imaruí
authors.initials: I
authors.lastname: Costa
authors.forename: Denise Bousfield
authors.initials: DB
authors.lastname: Silva
authors.forename: Maria Lydia
authors.initials: ML
authors.lastname: D'Andrea
authors.forename: Vitória P
authors.initials: VP
authors.lastname: Pinheiro
authors.forename: Maria Lucia M
authors.initials: ML
authors.lastname: Lee
authors.forename: Fernando
authors.initials: F
authors.lastname: Werneck
authors.forename: Mariana
authors.initials: M
authors.lastname: Emerenciano
authors.forename: Maria S
authors.initials: MS
authors.lastname: Pombo-de-Oliveira
mesh_terms: D001938:Brazil / Q000453:epidemiology; D020732:Cytogenetic Analysis / Q000379:methods; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D050982:GATA1 Transcription Factor / Q000235:genetics; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D007938:Leukemia / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics*; D007947:Leukemia, Megakaryoblastic, Acute / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D008297:Male; D017720:Molecular Epidemiology; D009154:Mutation; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; C497422:KMT2A protein, human; D015514:Oncogene Proteins, Fusion; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D018631:ras Proteins
keywords: Congenital acute lymphoblastic leukemia; FLT3; GATA1; KNRAS; MLL; PTPN11; acute myeloid leukemia