Restoration of Th1 cytokine synthesis by T cells of patients with chronic myelogenous leukemia in cytogenetic and hematologic remission with interferon-alpha

Chronic myelogenous leukemia (CML) is a disorder of the hematopoietic stem cell that results in malignant expansion of myeloid cells with a cytogeneti c abnormality, the translocation between chromosomes 9 and 22 known as the Philadelphia chromosome, Treatment with IFN-alpha has proven to be an effec tive therapy, inducing cytogenetic remission in CML patients. However, it i s unknown whether IFN-alpha can restore normal immune function for patients who achieve a complete cytogenetic remission. To address this question, we used a method of intracellular staining and flow cytometric analysis to as cribe the syntheses of Th1 or Th2 cytokines to T-cell subsets of patients i n chronic, in accelerated and in blast crisis phases as well as patients wh o had achieved a complete cytogenetic remission with IFN-alpha. We assessed the cytoplasmic synthesis of cytokine in phorbol ester (phorbol 12-myrista te 13-acetate)-activated CD4+ and CD8+ T-cell subsets of 81 patients with v arious stages of CML and 21 normal controls. The percentages of CD4+ and CD 8+ T cells from patients in chronic, in accelerated, and in blast crisis ph ases that synthesized Th1 cytokines interleukin (IL)-2, IFN-gamma, and tumo r necrosis factor-alpha were significantly lower than those of remission pa tients and normal controls. Conversely, the percentages of CD4+ and CD8+ T cells of patients in chronic, in accelerated, and in blast crisis phases of CML preferentially synthesized the Th2 cytokine IL-10, Patients who achiev ed a durable complete cytogenetic remission for >2 years without maintenanc e IFN-alpha therapy restored their preference for a Th1 cytokine profile th at is necessary for efficient cytotoxic T-cell function.