title: Genetic mutation and early onset of T-cell leukemia in pediatric patients infected at birth with HTLV-I.
abstract: T-cell leukemia/lymphoma (T-c LL) associated with prior infection with HTLV-I is rarely described in children. We present herein, the clinical, morphological, and virologic features of T-c LL, which occurred in eight pediatric cases with similar features of ATLL described in adults. There were three girls and five boys with age ranging from 2 to 18 years. Lymphoadenopathy, hepatosplenomegaly and marked skin lesions were presented in all cases. Five patients had hypercalcemia. The diagnostic criteria of T-c LL were based on both morphological and immunophenotypical analyses characterized by T-cell markers positively. Seven cases were cCD3+, CD4/CD25+, whereas CD1a and TdT were negative in all cases tested. HTLV-I antibodies were detected in all cases. HTLV-I provirus integration of at least one provirus was seen in all cases tested by molecular analysis. Mother-to-child transmission of HTLV-I was demonstrated in six cases. Interestingly, a homozygous deletion in p16 gene locus was observed in all four cases studied, while exons 7 and 8 of p53 were deleted in one child. The deletion of the p16(INK4A)/p14(ARF) or mutation of p53, key regulatory protein of cell cycle checkpoint in G1/S progression, found in five of the eight pediatric patients suggests that in these cases genetic lesions associated with HTLV-I infection may predispose for an early onset of leukemia.
authors.affiliation: Laboratorio de Marcadores Celulares and Hematology Service, Instituto Nacional de Cancer, Praca Cruz Vermelha 23, CEP 20230-130 Rio de Janeiro, Brazil. mpombo@inca.org.br
authors.forename: Maria S
authors.initials: MS
authors.lastname: Pombo-de-Oliveira
authors.forename: Jane A
authors.initials: JA
authors.lastname: Dobbin
authors.forename: Paula
authors.initials: P
authors.lastname: Loureiro
authors.forename: Davimar
authors.initials: D
authors.lastname: Borducchi
authors.forename: Raquel C
authors.initials: RC
authors.lastname: Maia
authors.forename: Marcia A
authors.initials: MA
authors.lastname: Fernandes
authors.forename: Geraldo B
authors.initials: GB
authors.lastname: Cavalcanti
authors.forename: Shigeki
authors.initials: S
authors.lastname: Takemoto
authors.forename: Genoveffa
authors.initials: G
authors.lastname: Franchini
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D015139:Blotting, Southern; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005091:Exons / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D019942:Genes, p16; D016158:Genes, p53; D015490:HTLV-I Infections / Q000150:complications / Q000151:congenital* / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000302:isolation & purification; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000150:complications / Q000453:epidemiology* / Q000235:genetics / Q000821:virology; D008297:Male; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000302:isolation & purification; D012867:Skin / Q000473:pathology; D013163:Splenomegaly / Q000209:etiology; D016019:Survival Analysis