RESUMO
BACKGROUND: Activating mutations of the FLT3 receptor tyrosine kinase are common in acute promyelocytic leukemia (APL) but have uncertain prognostic significance. Information regarding FLT3 expression levels in APL without FLT3 mutations is lacking. MATERIALS AND METHODS: Using RT-PCR, mutation analysis of the FLT3 gene, regarding internal tandem duplications (ITDs) and codon 835-836 point mutations, was performed and real-time PCR was carried out to determine the level of FLT3 expression in 11 APL patients at diagnosis and 5 in haematological remission with molecularly detectable disease. RESULTS: High levels of FLT3 transcript, at least a 10-fold increase compared to the normal controls, were found at diagnosis in all 3 mutated cases and in 2 patients without detectable FLT3 mutations. CONCLUSION: FLT3 overexpression can be documented in patients without FLT3 mutations. These patients might benefit from treatment using specific FLT3 tyrosine kinase inhibitors. Larger studies are needed to evaluate the clinical and biological significance of FLT3 overexpression in the absence of FLT3 mutations.
Assuntos
Leucemia Promielocítica Aguda/genética , Mutação Puntual , Tirosina Quinase 3 Semelhante a fms/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/metabolismo , Códon , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/metabolismo , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Proteínas de Fusão Oncogênica/biossíntese , Proteínas de Fusão Oncogênica/genética , Projetos Piloto , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Sequências de Repetição em Tandem , Tirosina Quinase 3 Semelhante a fms/biossínteseRESUMO
A case of adult osteopetrosis Type I was diagnosed in a 22-year-old female. She presented for investigation of anaemia with 'myelophthisic' characteristics and extramedullary haemopoiesis which was resistant to haematinics, nandrolone and low-dose corticosteroids. She became progressively transfusion-dependent with gradually worsening thrombocytopenia. She was successfully treated with recombinant erythropoietin. Anaemia as well as thrombocytopenia were corrected. There appeared to be a synergistic action of erythropoietin with steroids.