Improved biochemical assay for terminal deoxynucleotidyl transferase in human blood cells: Results in 89 adult patients with lymphoid leukemias and malignant lymphomas in leukemic phase

Abstract

Ion filtration chromatography of crude cell homogenates on DEAE-Sephadex allows determination of terminal deoxynucleotidyl transferase (TdT) activity in 10 6 blast cells from acute lymphoblastic leukemia (ALL) and in 2 × 10 7 normal bone marrow (BM) cells. Ninety-seven determinations of TdT in 40 patients with ALL during various stages of their disease revealed high levels of activity in BM and peripheral blood samples from all patients studied at diagnosis and in relapse. In 10 34 BM samples from patients with ALL in remission, levels of TdT activity were found to be significantly elevated as compared to normal controls. The remaining cases exhibited TdT activities within the normal range. In 20 patients with non-Hodgkin's lymphomas of null and T cell type in leukemic phase, TdT activities were within the same range as observed in active ALL. Eighteen of these had a histological diagnosis of diffuse poorly differentiated lymphoma of lymphoblastic type, one of giant follicular lymphoma and one of diffuse histiocytic lymphoma. In two patients with unclassifiable lymphoproliferative diseases of T cell type, no TdT activity was found, possibly indicating a disease of mature T cells. All 27 patients with lymphoid neoplasias of B cell type were found to exhibit no TdT activity in involved tissues. Determination of TdT activity appears to be a sensitive assay for detection of subclinical bone marrow involvement in TdT positive lymphoproliferative diseases. The clinical and theoretical significance of these observations is discussed.