Cytokine deregulation in hematological malignancies: clinical and biological implications

Endogenous cytokines are aberrantly produced in many cancers and serve as autocrine growth factors or indicators of immune response to the tumors. Hence, cytokine deregulation is likely to participate in the development or evolution of the malignant process. Over the last few years, we have performed a series of studies, with the objective of measuring cytokine levels in tumors and correlating endogenous levels with phenotypic manifestations of cancer and with prognosis. Here, we present our analysis of serum interleukin 6 (IL-6) levels in lymphomas. We demonstrate that IL-6 levels are elevated in both relapsed and newly diagnosed Hodgkin's and non-Hodgkin's lymphoma and that these levels correlate with established prognostic features. Furthermore, in diffuse large cell lymphoma, IL-6 is an independent prognostic variable for both complete remission and failure-free survival. The molecular mechanisms underlying cytokine deregulation are now being investigated, with preliminary data from our laboratory suggesting heterogeneous genetic driving forces. In some cases, oncogene aberrations, particularly in the RAS system, may be responsible.