Rearrangement of Both Immunoglobulin and T-Cell Receptor Genes in a Prolymphocytic Variant of Hairy Cell Leukemia Patient Resistant to Interferon-Alpha

We describe a patient with the so-called “prolymphocytic variant” form of hairy cell leukemia (HCL) resistant to treatment with interferon-α(IFN-α). Analysis of immunoglobulin (Ig) and T-cell receptor-β(TCRβ) gene rearrangements from serial peripheral blood mononuclear cell specimens (MNCs) confirmed not only the B-cell nature of the disease, but also the subsequent emergence of a morphologically indistinguishable population of cells with a clonal TCRi rearrangement in addition to the original Ig gene rearrangement. With the exception of a transient increase in peripheral blood T cells during treatment with deoxycoformycin (DCF), the MNCs remained essentially constant throughout therapy with no evidence of a co-existing T-cell clone to account for the TCRβrearrangement. Although NCs from this patient bound significantly less IFN-αthan did MNCs from other HCL patients, the binding was of high affinity with a kd similar to that of control cells. The number of IFN-γreceptors on our patient’s MNCs was four times higher than the number of IFN-αreceptors and was similar to the number of IFN-αreceptors on MNCs from HCL patients responsive to IFN-α. While various treatments including IFN-α, DCF, chlorambucil, splenectomy, leukopheresis, and IFN-γwere not able to change the clinical progression of the disease, they may have provided an opportunity for the divergent TCRβrearranged clone to expand and displace the initially dominant clone.