RESUMO
Differentiation between reactive bone marrow suppression due to viral infection and early stages of leukemia can be difficult particularly in young infants. We report on a 2-month-old girl presenting with pancytopenia and positive markers for congenital cytomegalovirus (CMV) infection. Definitive diagnosis of coexisting pro-B cell infant leukemia with cryptic MLL rearrangement was delayed by the transient regeneration of normal hematopoiesis and reduction of abnormal blastoid cells in the bone marrow following immunoglobulin administration. Molecular diagnosis could only be established using interphase fluorescence in situ hybridization (FISH) analysis which may be considered as a valuable additional diagnostic tool in similar cases.
Assuntos
Crise Blástica/terapia , Infecções por Citomegalovirus/terapia , Rearranjo Gênico , Imunoglobulinas Intravenosas/administração & dosagem , Leucemia de Células B/diagnóstico , Proteína de Leucina Linfoide-Mieloide/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Medula Óssea/patologia , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/congênito , Feminino , Citometria de Fluxo , Histona-Lisina N-Metiltransferase , Humanos , Hibridização in Situ Fluorescente , Lactente , Leucemia de Células B/genética , Pancitopenia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genéticaRESUMO
Chromosome abnormalities of 6q are not frequently observed in myeloid disorders. In this article, we report the incidence of these chromosome changes in childhood myeloid leukemia as 2%-4% based on the cytogenetic database of a single institution. We applied fluorescence in situ hybridization (FISH) to characterize precisely the types of 6q abnormalities in seven patients (six with acute myeloid leukemia and one with myelodysplastic syndrome). They carried various translocations involving different breakpoints in 6q, as confirmed by FISH using a whole-chromosome-6 paint. Four cases were reported as t(6;11), although the breakpoints varied. Among these, we identified a novel translocation, t(6;11)(q24.1;p15.5), in a patient with acute megakaryoblastic leukemia. Molecular cytogenetic studies using the PAC clone RP5-1173K1 localized the genomic breakpoint on chromosome 11 to within the NUP98 gene. The breakpoint on chromosome 6 was narrowed down to a 500-kb region between BAC clones RP11-721P14 and RP11-39H10. Reverse-transcription PCR was performed using a forward primer specific for NUP98 and a reverse primer for the candidate gene in the 500-kb interval in 6q. This experiment resulted in the identification of a new fusion between NUP98 and C6orf80. Further studies will aim to fully characterize C6orf80 and will elucidate the role of this new NUP98 fusion in myeloid leukemia.
Assuntos
Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 6/genética , Leucemia Mieloide/genética , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Proteínas de Fusão Oncogênica/genética , Translocação Genética , Doença Aguda , Adolescente , Sequência de Aminoácidos , Sequência de Bases , Criança , Pré-Escolar , Quebra Cromossômica , Cromossomos Artificiais Bacterianos , Análise Citogenética , DNA de Neoplasias/análise , Humanos , Hibridização in Situ Fluorescente , Lactente , Dados de Sequência Molecular , RNA Neoplásico/análise , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Malignancies from the Ewing family of tumors and acute lymphoblastic leukemia (ALL) are not known to be associated with each other. A 5-year-old girl was incidentally found to suffer from acute lymphoblastic leukemia during bone marrow staging for Ewing sarcoma of the radius. The simultaneous presence of two distinct neoplasms was confirmed by RT-PCR, with EWS/FLI1 type 1 rearrangement in the bone tumor and TEL/AML1 rearrangement in the marrow. She was treated with chemotherapy, radiotherapy, and surgery and was in remission of both diseases 31 months after diagnosis.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Sarcoma de Ewing/complicações , Pré-Escolar , Terapia Combinada , Subunidade alfa 2 de Fator de Ligação ao Core , Intervalo Livre de Doença , Feminino , Humanos , Proteínas de Fusão Oncogênica , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Proteína Proto-Oncogênica c-fli-1 , Proteína EWS de Ligação a RNA , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/terapia , Translocação GenéticaAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteínas de Ligação a DNA/genética , Proteínas Ativadoras de GTPase/genética , Leucemia Mieloide Aguda/diagnóstico , Proteínas de Fusão Oncogênica/genética , Proto-Oncogenes/genética , RNA Mensageiro/genética , Fatores de Transcrição/genética , Citarabina/administração & dosagem , Etoposídeo/administração & dosagem , Histona-Lisina N-Metiltransferase , Humanos , Idarubicina/administração & dosagem , Hibridização in Situ Fluorescente , Lactente , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Masculino , Mitoxantrona/administração & dosagem , Proteína de Leucina Linfoide-Mieloide , Neoplasia ResidualAssuntos
Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 2/genética , Mutação/genética , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Recombinação Genética/genética , Sequência de Bases/genética , Feminino , Humanos , Lactente , Dados de Sequência Molecular , Proteína de Leucina Linfoide-MieloideRESUMO
The translocation t(8;21)(q22;q22), which results in the fusion of the AML1 (RUNX1) and ETO (CBFA2T1) genes, is a recurrent aberration in acute myeloid leukemia (AML), preferentially correlated with FAB M2, and has the highest incidence in childhood AML. Because of the favorable prognosis, the evidence of the t(8;21) or the AML1/ETO fusion gene is mandatory in most of the therapy trials, allowing the stratification of the patients to the correct risk group in terms of treatment. Here we present six out of 59 children with AML who were positive for AML1/ETO by RT-PCR, but showed no evidence of the classical t(8;21)(q22;q22) by conventional cytogenetics. Because of the discrepancies between molecular and cytogenetic analyses, these six patients were further investigated by fluorescence in situ hybridization analysis. Small hidden interstitial insertions resulting in an AML1/ETO rearrangement were detected in five (8.5%) of the 59 patients, whereas the sixth patient showed a cryptic three-way translocation. The insertions could be characterized as ins(21;8) in three patients and ins(8;21) in the remaining two. Additionally, three of the patients showed secondary chromosome aberrations leading to a higher complexity of the karyotype. In conclusion, the combination of more than one standard technique in the analysis of AML1/ETO is useful to reveal the overall frequency of cryptic chromosome rearrangements and permits a better understanding of the mechanisms involved in the generation of this fusion gene.
