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Restoration of Th1 Cytokine Synthesis by T Cells of Patients with Chronic Myelogenous Leukemia in Cytogenetic and Hematologic Remission with Interferon-

Departments of Laboratory Medicine [J. M. R., B-N. L., H. J., H. F.], Leukemia [H. M. K.], and Bioimmunotherapy [M. T.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Chronic myelogenous leukemia (CML) is a disorder of the hematopoietic stem cell that results in malignant expansion of myeloid cells with a cytogenetic abnormality, the translocation between chromosomes 9 and 22 known as the Philadelphia chromosome. Treatment with IFN- has proven to be an effective therapy, inducing cytogenetic remission in CML patients. However, it is unknown whether IFN- 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 ascribe the syntheses of Th1 or Th2 cytokines to T-cell subsets of patients in chronic, in accelerated, and in blast crisis phases as well as patients who had achieved a complete cytogenetic remission with IFN-. We assessed the cytoplasmic synthesis of cytokine in phorbol ester (phorbol 12-myristate 13-acetate)-activated CD4+ and CD8+ T-cell subsets of 81 patients with various stages of CML and 21 normal controls. The percentages of CD4+ and CD8+ T cells from patients in chronic, in accelerated, and in blast crisis phases that synthesized Th1 cytokines interleukin (IL)-2, IFN-, and tumor necrosis factor- were significantly lower than those of remission patients 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 achieved a durable complete cytogenetic remission for >2 years without maintenance IFN- therapy restored their preference for a Th1 cytokine profile that is necessary for efficient cytotoxic T-cell function.

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