RESUMO
The optimal management of malignant haematological disorders depend on the degree of tumor load reduction after therapy. Chronic myeloid leukemia constitutes a clinical model for molecular detection and therapy surveillance of malignant disease since this entity was the first leukemia shown to be associated with a specific bcr-abl fusion gene in the patient's leukemia cells. Molecular monitoring of bcr-abl transcript levels by real-time quantitative PCR is increasingly used to assess treatment response in patients with chronic myeloid leukemia (CML). This has become particularly relevant in the era of imatinib therapy when residual levels of leukaemia usually fall below the level of detection by bone marrow cytogenetic analysis. We monitored bcr-abl transcript levels by quantitative real time PCR in 50 tunisian patients treated with imatinib for chronic myeloid leukemia in chronic phase for a median of 29 months (3-60) after they started imatinib.
Assuntos
Proteínas de Fusão bcr-abl/genética , Leucemia Mieloide de Fase Crônica/sangue , RNA Mensageiro/análise , RNA Neoplásico/sangue , Adulto , Antineoplásicos/uso terapêutico , Benzamidas , Sistemas Computacionais , Feminino , Seguimentos , Proteínas de Fusão bcr-abl/biossíntese , Humanos , Mesilato de Imatinib , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Leucemia Mieloide de Fase Crônica/genética , Leucemia Mieloide de Fase Crônica/patologia , Masculino , Neoplasia Residual , Piperazinas/uso terapêutico , Reação em Cadeia da Polimerase , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Carga Tumoral , TunísiaRESUMO
Hypereosinophilic syndromes (HES) are a heterogeneous group of disorders characterized by marked peripheral blood and tissue eosinophilia resulting in organ damage. Recent advances in molecular biology have led to the identification of a FIP1L1-PDGFRA fusion gene as a recurrent abnormality in some patients with HES. This fusion gene results from a cryptic 4q12 interstitial deletion involving an 800 kb region. Recent reports indicate that this subtype of HES is imatinib responsive with rapid and complete haematological remissions. Here we report two patients successfully treated with imatinib.
Assuntos
Síndrome Hipereosinofílica/tratamento farmacológico , Proteínas de Fusão Oncogênica/efeitos dos fármacos , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/efeitos dos fármacos , Fatores de Poliadenilação e Clivagem de mRNA/efeitos dos fármacos , Adulto , Benzamidas , Humanos , Síndrome Hipereosinofílica/genética , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
The molecular analysis of chromosomal abnormalities associated with hematological malignancies allowed the identification of genes involved in theses rearrangements as well as of some recurrent mechanisms. Polymerase chain reaction (PCR) tools are now available to detect these rearrangements, allowing a better follow-up of these diseases. Chronic myeloid leukemia is a myeloproliferative disorder characterized by a reciprocal translocation t(9;22)(q34;q11) which results in a bcr-abl fusion gene. Retro-transcription polymerase chain reaction (RT-PCR) is used to detect bcr-abl to establish diagnosis and to monitor patients. We report here the results of 30 patients samples tested in the hematology laboratory at Pasteur Institute, diagnosed as chronic myeloid leukemia and monitored with RT-PCR. Our results highlight the interest of molecular tools to diagnose and monitor patients mainly when cytogenetic techniques are irrelevant such as cases with complex chromosomal rearrangements or when patients achieve Philadelphia negativity after treatment.
Assuntos
Cromossomos Humanos Par 22/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Translocação Genética/genética , Adolescente , Adulto , Exame de Medula Óssea , Análise Citogenética , Eletroforese em Gel de Ágar , Feminino , Proteínas de Fusão bcr-abl/genética , Humanos , Cariotipagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa/normas , Sensibilidade e Especificidade , TunísiaRESUMO
Hypereosinophilic syndromes (HES) are a heterogenous group of rare disorders characterized by sustained and otherwise unexplained overproduction of eosinophils with organ involvement and consecutive dysfunction. Detection of the FIP1L1-PDGFRA fusion gene or the corresponding cryptic 4q12 deletion in HES supports the diagnosis of chronic eosinophilic leukemia (CEL) and provides a molecular explanation for the pathogenesis of this disorder. We screened seven Tunisian patients fulfilling the WHO criteria of HES for the presence of the FIP1L1-PDGFRA fusion gene using nested reverse transcription polymerase chain reaction on peripheral blood samples. Four of the seven patients were positive for this fusion gene. Sequence analysis revealed a substantial heterogeneity of the fusion transcripts due to the involvement of several FIP1L1 exons. All patients were male. The median age at diagnosis was 24 years (range, 18-50); one patient had a history of hypereosinophilia of more than 10 years. Two patients had clinically important and symptomatic eosinophilic endomyocardial disease with thrombotic events. Splenomegaly was constant in FIP1L1-PDGFRA positive CEL but not in the other HES patients (only 1/3).