RESUMO
Translocation t(8;21)(q22;q22) is a common karyotypic abnormality detected in about 15% of acute myeloid leukemia (AML) cases. The rearrangement results in fusion of the RUNX1 (also known as AML1) and CBFA2T1 (also known as ETO) genes, generating a 5'RUNX1/3'CBFA2T1 transcriptionally active fusion gene on derivative chromosome 8, but some cases with ins(21;8) and ins(8;21) have been observed. However, a detailed breakpoint characterization of the insertion events has never been reported. In the present article, we describe six insertion events among 82 (7.3%) AML cases characterized by the RUNX1/CBFA2T1 fusion. Using FISH experiments with appropriate bacterial artificial chromosome (BAC) and P1 artificial chromosome (PAC) probes, we were able to perform a detailed molecular cytogenetic characterization of one case with ins(8;21) and five with ins(21;8). Our analysis revealed that insertions generating the 5'RUNX1/3'CBFA2T1 gene showed variable breakpoints; the size of the inserted elements ranged from 2.4 to 44 Mb.
Assuntos
Proteínas de Ligação a DNA/genética , Leucemia Mieloide Aguda/genética , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas/genética , Fatores de Transcrição/genética , Subunidade alfa 2 de Fator de Ligação ao Core , Humanos , Hibridização in Situ Fluorescente , Proteína 1 Parceira de Translocação de RUNX1 , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Translocação GenéticaRESUMO
We describe a case of acute myeloid leukemia (AML) with t(8;21) in which complete remission (CR) was obtained with G-CSF given at 10 microg/kg in the absence of concomitant cytotoxic chemotherapy. CR was achieved following 2 weeks of therapy and confirmed by investigating minimal residual disease by four-color flow cytometry analysis. During treatment with G-CSF, maturing cells with cytoplasmic Auer Rods were observed in the peripheral blood, suggesting a differentiation effect. This case adds further evidence for a specific role of G-CSF in the treatment of AML with t(8;21), namely in patients who are not eligible for aggressive chemotherapy.
Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Leucemia Mieloide/tratamento farmacológico , Doença Aguda , Medula Óssea/patologia , Cromossomos Humanos Par 21 , Cromossomos Humanos Par 8 , Feminino , Citometria de Fluxo , Humanos , Imunofenotipagem , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/genética , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Indução de Remissão , Terapia de Salvação , Translocação Genética , Resultado do TratamentoAssuntos
Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Humanos , Lactente , Proteína de Leucina Linfoide-Mieloide , Proteínas Nucleares/química , Proteínas Nucleares/genética , Proteínas de Fusão Oncogênica/química , Estrutura Terciária de Proteína , Ativação Transcricional , Fatores de Elongação da Transcrição , Translocação GenéticaRESUMO
OBJECTIVES: To evaluate therapeutic results and prognostic factors from a series of 44 patients affected by de novo acute myeloid leukemia with multilineage dysplasia (MD-AML), treated with the combination of fludarabine, cytarabine and G-CSF (FLAG). METHODS: Forty-four patients with de novo MD-AML were treated with the FLAG regimen. The median age was 61 yr (range 31-75 yr). Induction therapy consisted of the FLAG regimen; consolidation included idarubicin plus cytarabine. Patients with a compatible donor and aged less than 55 yr were programmed to receive allogeneic bone marrow transplantation (BMT), while in those without a donor and aged less than 65 yr autologous transplantation with peripheral blood stem cells mobilized by a consolidation regimen plus G-CSF was planned. Bone marrow harvest was performed in poor mobilizers. RESULTS: Complete remission (CR) was achieved in 28 out of 44 patients (64%). Death in induction occurred in four patients (9%), while 12 patients (27%) were resistant to FLAG. Toxicity of consolidation was negligible. Most patients aged less than 60 yr and achieving CR were eligible for transplantation procedures, the main reason of exclusion being early relapse. Median overall survival and disease free survival were 16 and 22 months, respectively. Unfavorable cytogenetics was the only parameter significantly related to inferior clinical outcome following multivariate analysis. CONCLUSION: Multilineage dysplasia per se is not an adverse prognostic factor in AML patients treated with the FLAG regimen. Favorable results are obtained in patients with intermediate karyotype, while in those with adverse cytogenetics new approaches are clearly needed. The toxicity of the regimen is also acceptable in the elderly, and following induction/consolidation, most patients may be submitted to transplantation procedures.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Citarabina/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Leucemia Mieloide/patologia , Leucemia Mieloide/terapia , Vidarabina/administração & dosagem , Adulto , Idoso , Transplante de Medula Óssea , Linhagem da Célula , Terapia Combinada , Feminino , Mobilização de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Transplante Homólogo , Vidarabina/análogos & derivadosRESUMO
Seventeen patients affected by acute myeloid leukemia (AML) with t(8;21) were prospectively programmed to receive three courses of high-dose cytarabine (HDARA-C) as post-remission therapy. The median age was 39 years and in all cases t(8;21) was the only karyotypic abnormality. Complete remission (CR) was achieved in 14 out of 17 cases (82%) and, after first consolidation with NOVIA regimen (intermediate dose ARA-C plus mitoxantrone), all patients received the three planned courses of HDARA-C (3g/m(2) q12h on days 1, 3, 5). There were two documented infections, while all patients experienced fever of unknown origin (FUO). Nonhematological toxicity was mild. Thirteen out of 14 patients are in continuous CR after a median follow-up of 44 months. One patient relapsed at 16 months and, following CR2 achievement, underwent allogeneic transplantation; he died 3 months later while in CR from acute graft versus host disease (GVHD). Survival at 5 years is projected at 79%. Our data confirm the efficacy of repeated courses of HDARAC for patients with t(8;21) AML.
