Establishment of an interleukin-3-dependent leukemic cell line from a patient with chronic lymphocytic leukemia in the acute phase

Abstract

A novel human leukemic cell line, TMD2, which proliferates dependently on interleukin-3 (IL-3), was established from the peripheral blood (PB) of a patient with chronic lymphocytic leukemia (CLL) in the acute phase. After 8 years of the chronic phase of CLL, lymphoblastoid cells appeared and became dominant in the PB. After repeated subcultures of the patient's PB cells in the acute phase, lymphoblastoid cells have proliferated actively in the presence of recombinant human IL-3, and the TMD2 cell line has been established. The lymphoblastoid cells in acute phase and TMD2 cells proliferated dependently on IL-3, whereas growth of the small lymphocytes in chronic phase was not supported by IL-3. Other ILs (IL-1, 2, and 4 through 6) or CSF did not support the growth or survival of TMD2 cells. The existence of high-affinity receptors for IL-3 was shown on TMD2 cells (binding sites 88 per cell, Kd = 76.9 pmol/L). DNA extracted from the small lymphocytes in the chronic phase, the lymphoblastoid cells in the acute phase, and TMD2 cells showed the same rearrangement pattern of the immunoglobulin heavy- chain gene. Therefore, these cells were considered to have originated from the same clone. These results imply that a genetic event that caused the responsiveness to IL-3 in the cell of the chronic phase caused the acute transformation of CLL in this patient. We consider that TMD2 cell line is valuable as a model of cells of CLL in the acute phase and as a tool for studying the signal transduction system of IL-3.