Perfil de expresión génica de citoquinas pro-inflamatorias de pacientes con leucemia mieloide crónica en respuesta al tratamiento con imatinib

Imatinib represents the current first-line therapy for chronic myeloid leukaemia (CML) patients. Besides its direct action targeting BCR-ABL1, imatinib may also influence the anti-tumour response. However, there are few studies that evaluate possible immune-pathological events related to the expression of pro-inflammatory cytokines at diagnosis and during treatment. Therefore, our aim was to describe the dynamic of TNF, IFNG and IL6 gene expression regarding molecular response to imatinib. This study included 161 peripheral blood samples from 92 CML patients (34 serially followed) who were analysed according to the molecular response to imatinib, and 26 from healthy donors. An aliquot of the stored sample used to monitor %BCR-ABL1 was used to quantify the expression of cytokine genes by real time PCR. Our results show a significant decrease in the gene expression of TNF, IFNG and IL6 in patients at diagnosis compared with healthy controls. Also, a significant increase in TNF and IL6 was observed in those patients who achieved the optimal molecular response at the different time points on imatinib therapy. Despite the peripheral levels of TNF, IFNG and IL6 genes may not reflect the tumour microenvironment, the dynamic of cytokine gene expression may account for a systemic anti-CML immune response according to the molecular response to imatinib. In conclusion, our results are in agreement with a significant immune suppression in CML patients at diagnosis and an initial stimulatory effect on the immune system after imatinib initiation, especially in responder patients.