Cytokines and soluble HLA-G levels in bone marrow stroma and their association with the survival rate of patients exhibiting childhood T-cell acute lymphoblastic leukemia

Leukemic cells can induce defective expression of soluble factors and change marrow cytokine profile, leading to aberrant cell signaling, cell fixation and cell proliferation in bone marrow. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disorder which accounts for 15% of pediatric ALL. To evaluate the contribution of immunological factors on T-ALL survival, we measured Th1, Th2, Th17 cytokines and soluble HLA-G (sHLA-G) levels in bone marrow from 32 Brazilian children at diagnosis (D0), after induction (D19) and after consolidation (D49) of the chemotherapy phase. Data were analyzed using non-parametric tests, and survival rates were evaluated by Kaplan-Meier method (log-rank test). TNF, IL-10 and IL-6 levels were increased at diagnosis compared to D19 and D49. IL-10 levels < 4.57 pg/mL at diagnosis were associated with increased survival rate, in presence of positive correlation between IL-2 and IL-17 levels. Increased survival rate was also associated with IFN-γ levels < 1.17 pg/mL at D49, with a positive correlation observed between IL-4 and IL-2 as well IL-4 and IL-17 levels. In contrast, worse survival rate was associated with IL-2, IL-4 and IL-10 levels imbalance. In addition, increased sHLA-G levels at diagnosis were associated with increased leukocyte count, a well-known factor for poor prognosis. In conclusion, cytokines and sHLA-G play an essential role in marrow T-ALL microenvironment during chemotherapy, especially the immunosuppressive cytokine IL-10 which can be used as biomarker of disease outcome, being also a potential target for novel T-ALL treatments.