Cytokine Syntheses by T-Cell Subsets From Chronic Myeloid Leukemia Patients: Relationship Between Pre-Treatment Levels and Response to Imatinib Therapy

Background: Although T-cell cytokine's role in the long-term control of chronic myeloid leukemia (CML) is well established, previous studies showed contradicting results regarding imatinib (IM) effect on the endogenous T-cell function by IM. The purpose of this study was to determine the relation between the endogenous T-cell function prior to therapy and the degree of response to IM therapy in CP CML. In addition, modulation of the endogenous T-cell function during IM therapy was studied. Methods: We evaluated Th1 (gamma interferon (IFN-gamma)), Th2 (interleukin (IL-4)) and tumor necrosis factor (TNF)-alpha cytokine synthesis by activated T-cell subsets in 20 patients with newly diagnosed CML in chronic phase (CP CML) using flow cytometry before and during IM therapy compared to patients with IM resistance (IM Res) and healthy donors. Results: Patients with optimal response (CML OR) to IM demonstrated a lower pre-treatment Th1 cytokine compared to that of healthy donors, and a higher percentage of Th2 and TNF-alpha producing T cells compared to that of healthy donors, non-optimal responders (CML nOR) and those with IM Res. A shift from Th2 profile to Th1 profile and initial decline of TNF-alpha producing T cells was detected early during therapy in optimal responders which was coinciding with complete hematological remission with a significant increase in the percentages of CD4+ve/IFN-gamma+ve cells (P = 0.01) and a significant drop of in CD8+ve/IL-4+ve T cells (P = 0.04). Conclusion: We believe that pre-treatment levels of IL-4 and/or TNF-alpha may have a role in identifying CP CML patients who may respond to IM therapy; however, further investigation is needed.