RESUMO
We applied multicolor spectral karyotyping (SKY) to a panel of 29 newly diagnosed pediatric pre B-cell ALLs with normal and abnormal G-banded karyotypes to identify cryptic translocations and define complex chromosomal rearrangements. By this method, it was possible to define all add chromosomes in six cases, a cryptic t(12;21)(p13;q11) translocation in six cases, marker chromosomes in two cases and refine the misidentified aberrations by G-banding in two cases. In addition, we identified five novel non-recurrent translocations - t(2;9)(p11.2;p13), t(2;22) (p11.2;q11.2), t(6;8)(p12;p11), t(12;14)(p13;q32) and t(X;8)(p22.3;q?). Of these translocations, t(2;9), t(2;22) and t(12;14) were identified by G-banding analysis and confirmed by SKY. We characterized a t(12;14)( p13;q32) translocation by FISH, and identified a fusion of TEL with IGH for the first time in ALL. We identified a rearrangement of PAX5 locus in a case with t(2;9)(p11.2;p13) by FISH and defined the breakpoint telomeric to PAX5 in der(9)t(3;9)(?;p13). These studies demonstrate the utility of using SKY in combination with G-banding and FISH to augment the precision with which chromosomal aberrations may be identified in tumor cells.
Assuntos
Cromossomos Humanos/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Cariotipagem Espectral , Doença Aguda , Adolescente , Fusão Gênica Artificial , Criança , Pré-Escolar , Aberrações Cromossômicas , Bandeamento Cromossômico , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , Recém-Nascido , Masculino , Fator de Transcrição PAX5 , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Proteínas Proto-Oncogênicas c-ets , Proteínas Repressoras/genética , Fatores de Transcrição/genética , Translocação Genética , Variante 6 da Proteína do Fator de Translocação ETSRESUMO
Gilles de la Tourette's syndrome (GTS) is a genetic disorder characterized by multiple motor and vocal tics, obsessive-compulsive disorder, and attention-deficit disorder. Family studies support the presence of an autosomal dominant gene; however, to date, an assignment for the GTS locus has not been made. We present the case of a boy with GTS and a deletion of the terminal portion of the short arm of chromosome 9, del(9)(qter----p2304:).
Assuntos
Cromossomos Humanos Par 9 , Monossomia , Síndrome de Tourette/genética , Adolescente , Sondas de DNA , Humanos , Interferon Tipo I/genética , Cariotipagem , Masculino , Polimorfismo de Fragmento de Restrição , Síndrome de Tourette/complicaçõesRESUMO
An intensive regimen of combined etoposide (VP-16) and 5-azacitidine (5-Az) was used to treat 96 children and adolescents with refractory or relapsed acute nonlymphocytic leukemia (ANLL). Patients were given two sequential five-day courses of VP-16, 250 mg/m2 for three days, followed by 5-Az, 300 mg/m2 for two days. An additional five-day course was administered if marrow aplasia was not evident by day 13. A complete remission rate of 45% was achieved with a median of two courses of VP-16 and 5-Az. The outcome of induction therapy was not influenced by prior treatment, blast cell morphology, or disease status on study entry (refractory or relapsed). Twenty-seven patients have relapsed after remission periods of 35 to 920 days (median, 110 days); seven others are free of leukemia for up to 519 days. The effectiveness of VP-16/5-Az combination therapy in patients refractory to anthracyclines and cytarabine indicates a potential role for these compounds in first-line treatment of patients with ANLL.
