HISTONE H1 SUPPRESSES TUMOR-GROWTH OF LEUKEMIA-CELLS IN-VITRO, EX-VIVO AND IN AN ANIMAL-MODEL SUGGESTING EXTRACELLULAR FUNCTIONS OF HISTONES

Purified histone H1 exerts growth inhibition of leukemia cells indepen dent of lineage, stage, and maturation. At 200 mu g/ml, H1 proved cyto toxic in 19 of 21 of the tested leukemia-derived cell lines and for 11 of 16 of the fresh tumor samples from leukemia patients. In all cases , normal peripheral blood mononuclear cells and bone marrow cells rema ined unaffected. Multicellular spheroids from the Burkitt's lymphoma c ell line IM-9 were growth arrested at 500 mu g H1/ml. The clonogenic g rowth of the Burkitt's lymphoma cell line Daudi was arrested at 160 mu g H1/ml. Synthetic H1-peptides as well as peptides and proteins with biochemical properties similar to HI had no inhibitory growth effect a t equimolar concentrations. Furthermore, 250 mu g H1 injected into a B urkitt's lymphoma (Daudi), xenotransplanted into nude mice, arrested t umor growth. As shown by electron microscopy and flow cytometry, incub ation of leukemia cells with H1 resulted in severe plasma membrane dam age and ultimately cytolysis. This report characterizes a 33-kd protei n that binds H1 and is responsible for the cell death via destruction of the cell membrane integrity. New extranuclear functions of histones are presented.