Twenty five percent of patients in the chronic phase of chronic myelogenous leukemia (CML) are treated with interferon-α (IFN-α) to induce a cytogenic remission. In addition to its direct effects on leukemic cells, IFN-α has been shown to induce immunologic alterations, including upregulation of the expression of major histocompatibility (MHC) antigens in antigen-presenting cells (APCs), as well as augmentation of the activity of the lymphocytes against tumor cells. However, there has been little direct evidence supporting a causal interaction between cellular immunoreactivity and clinical responsiveness to IFN-α.

We have shown that one approach to elucidate the immunological mechanisms by which IFN-α exerts its anti-CML activity is by analyzing therapy-induced modulation in T-cell receptor (TCR) Vβ chain usage, using the reverse transcription-polymerase chain reaction (RT-PCR) followed by single-strand conformation (SSCP) analysis. This method is particularly attractive, since it provides an index of antigen-specific T cell expansion, but does not require the extraction and purification of the antigens involved in the T-cell response. T cell clones that express the Vβ 10, 12, and 14 families predominate in the peripheral blood (PB) of CML patients. The enhanced expression of the Vpβ and 20 families has been detected in IFN-α responsive patients but not patients who are poorly responsive to this agent. This suggests that expansion of T cells expressing these TCR Vβ gene families may serve as a prognostic factors of the clinical responsiveness of CML patients to IFN-α.

In addition, since T cell clones that express certain Vβ families may react with a discrete set of antigenic peptides presented on the surface of malignant cells, a better understanding of the immunobiology of T cells in CML may allow for the design of increasing efficacious immune therapy for this disease.