In Vitro Evaluation of Antiproliferative Activity of CCRF-CEM Supernatant on Lymphoid and Nonlymphoid Leukemic Cells
Several glycoproteins are able to inhibit cell proliferation in vitro and in vivo [1–4]. Some of these have been purified to homogeneity, cloned, sequenced (interferon, IFN-γ [5–7] and tumor necrosis factor, TNF [8–12], and utilized in clinical trials. T-lymphoblastic leukemic cells and actived T cells are the cellular lines mostly involved in the production of glycoproteins with antiproliferative properties. Recently, particular attention has been focused on two glycoproteins isolated from T-lymphoblastic cell line MT-1 and CCRF- GEM supernatants:CIL (colony inhibiting lymphokine) [13, 14] and TLSL (T-leukemia derived suppressor lymphokine) . CIL and TLSL have the same molecular weight and the same chemical-physical properties. They inhibit clonogenic activity and DNA synthesis of normal hemopoietic precursor cells as well as of a variety of malignant hemopoietic cells. However, not all leukemic cells are sensitive, showing heterogeneity of response. TLSL and CIL are cytostatic, and treated target cells accumulate either in G1 or S phase of the cell cycle. The cellular sensitivity to the inhibitory action of CIL has been correlated with expression on the cell membrane of HLA-Dr antigen. It particulary inhibits proliferation of human Epstein-Barr virus (EBV) transformed lymphoblastoid lines (HLA-Dr+) but is much less inhibitory on myeloid leukemic lines (HL-60, K-562). TLSL is also active on cell lines not expressing HLA-Dr antigen.
KeywordsCell Growth Inhibition Human Tumor Necrosis Factor Hemopoietic Progenitor Recombinant Human Tumor Necrosis Factor Human Tumor Necrosis Factor Alpha
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