Résumé
Chronic myeloid leukemia (CML) originates from the hematopoietic stem cell and is characterized by the reciprocal translocation t(9;22)(q34;q11), which results in the BCR-ABL fusion gene on chromosome 22q-, also known as the Philadelphia chromosome. This chimeric gene codes for a cytoplasmic protein with constitutive tyrosine-kinase activity, responsible for cellular transformation and leukemogenesis in CML. The aim of this observational cohort study was to discriminate and quantify BCR-ABL transcripts in the peripheral blood of patients with CML who were treated with imatinib mesylate (Glivec, Novartis). Twenty-two patients were followed for six months during treatment. Quantitative real time polymerase chain reaction was performed before treatment and after 3 and 6 months from treatment initiation. As compared with the third month, there was a significant decrease in BCR-ABL expression in the sixth month of treatment (P = 0.0002). At the sixth month, there was a significant difference in the levels of the two major transcripts of BCR-ABL, B2A2 and B3A2 (P = 0.0347), indicating that B2A2 may be more sensitive to imatinib. The results of our study indicate that imatinib is able to modify the natural history of CML, and raise the hypothesis that patients who express the B2A2 transcript may have a better prognosis.
Sujets)
Humains , Mâle , Femelle , Adulte , Adulte d'âge moyen , Sujet âgé , Antinéoplasiques/usage thérapeutique , Leucémie myéloïde chronique BCR-ABL positive/traitement médicamenteux , Pipérazines/usage thérapeutique , Pyrimidines/usage thérapeutique , Protéines de fusion bcr-abl/génétique , Transcription génétique/génétique , Analyse de variance , Études de cohortes , Facteurs temps , Leucémie myéloïde chronique BCR-ABL positive/génétique , Protéines de fusion bcr-abl/effets des médicaments et des substances chimiques , RT-PCR , Réaction de polymérisation en chaîne/méthodes , Résultat thérapeutique , Transcription génétique/effets des médicaments et des substances chimiquesRésumé
Os autores relatam um caso de leucemia linfoblástica aguda (ALL) que no exame citogenético de células da medula óssea apresentou manomalias cromossômicas já descritas nesta condiçäo del(6)(q23); t(9;22)(q34;q11), ao lado das alteraçöes cromossômicas del(4)(p14) + 4ace e t(4;15)(p14;pter) ainda näo relatadas em ALL. Discutem a hipótese destas alteraçöes influenciarem na origem da malignidade, na pobre resposta ao tratamento e mau prognóstico observado no paciente pela possível ativaçäo de oncogenes em consequência das anomalias observadas