Genetic mutation and early onset of T-cell leukemia in pediatric patients infected at birth with HTLV-I

• Published in: Leukemia research 2002-02, Vol.26 (2), p.155-161
• Main Authors: Pombo-de-Oliveira, Maria S., Dobbin, Jane A., Loureiro, Paula, Borducchi, Davimar, Maia, Raquel C., Fernandes, Marcia A., Cavalcanti, Geraldo B., Takemoto, Shigeki, Franchini, Genoveffa
• Format: Article
• Language: English
• Subjects: Adolescent; Age of Onset; Biological and medical sciences; Blotting, Southern; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Exons - genetics; Female; Gene Deletion; Genes, p16; Genes, p53; Hematologic and hematopoietic diseases; HTLV-I; HTLV-I Infections - complications; HTLV-I Infections - congenital; HTLV-I Infections - virology; Human T-lymphotropic virus 1; Human T-lymphotropic virus 1 - isolation & purification; Humans; Hypercalcemia - etiology; Leukemia-Lymphoma, Adult T-Cell - complications; Leukemia-Lymphoma, Adult T-Cell - epidemiology; Leukemia-Lymphoma, Adult T-Cell - genetics; Leukemia-Lymphoma, Adult T-Cell - virology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; p14 gene; p16 gene; p53 gene; Pediatric patients; Polymerase Chain Reaction; Proviruses - isolation & purification; Skin - pathology; Splenomegaly - etiology; Survival Analysis; T-cell leukemia
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/S0145-2126(01)00108-4

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.