Elena G. Bamberger

A Multipotential Leukemia Cell Line (K-562) of Human Origin

Abstract The K-562 leukemia cell line, originally established in our laboratory, has been characterized as an early precursor of the granulocytic series with a block for differentiation. Since K-562 blasts did not differentiate when cultured for 7-8 days in liquid media or 14-16 days in agar-gel an attempt was made to stimulate their potential for spontaneous differentiation by prolonging the time in culture. Inducers of differentiation were not added to the cultures and the cells were studied when they reached the steady state rather than during exponential growth. The cultivation of K-562 cells for 10 to 11 days in media gradually depleted of the essential nutrients needed for cell division induced their differentiation into early precursors of the monocytic, granulocytic, and erythrocytic series. Thus, the peroxidase reaction for hemoglobin demonstrates benzidine-positive material limited to the region of the Golgi apparatus. Analysis of the hemoglobin by isoelectric focusing indicated major bands in the region of embryonic hemoglobin. Most cells (80-90%) give a strong reaction for α-naphthyl acetate esterase typical of monocytes and as many as 30 to 40% of the cells have abundant red cytoplasmic granules of naphthol AS-D chloroacetate esterase characteristic of granulocytic precursors. Myeloperoxidase activity was found in 5 to 10% of the cells. Polyploid cells (5-8%) and early myelomonocytic precursors have PAS-positive material, were stained with Sudan black, and possessed abundant acid phosphatase. The data support the conclusion that K-562 is, indeed, a multipotential leukemia cell line of human origin.

Regulators of cell division: endogenous mitotic inhibitors of mammalian cells.

Publisher Summary This chapter deals with the antimitotic substances found in a variety of tissues and sera of humans and animals, as well as with inhibitors produced by cultured cells. It appears that cultured cells release substances which in turn inhibit cell division when the appropriate concentration in the medium is reached. Thus specific and nonspecific inhibitors of cultured cell growth have been reported. Some normal cells appear to produce an inhibitor of the proliferation of oncogenic virus-containing cells which are unable to synthesize a similar antimitotic substance. The growth of normal fibroblasts may be controlled by contact inhibition, protein factors present in the serum added to the medium, and attachment to rigid surfaces (anchorage-depending growth). Extracts from mice and chick embryos have been found to suppress cell growth in vivo andin vitro, respectively. The administration of mouse embryonic and placental extracts inhibited the growth of 70% of spontaneous and transplanted tumors. Since the treatment was mainly effective on carcinomas and not on sarcomas, the extract appeared to have some tissue specificity. Low-molecular weight inhibitors of normal cells have also been obtained from chick embryos. Specific and nonspecific mitotic inhibitors have been partially purified from mammalian and amphibian kidneys. The existence of a chalone, probably protein in nature, has been reported in amphibian kidneys. It may control growth and differentiation from the early stages of the pronephros, as well as kidney cell renewal in adult life. Numerous growth inhibitors isolated from the liver were active against various tumor cells both in vitro and in vivo.

Inhibition of human leukemia cell proliferation by dimethyl sulfoxide

Abstract The treatment with 1% and 2% DMSO produced reversible structural and functional changes in the K-562 human myelogenous cell line. These changes include: (a) inhibition of cell proliferation with decreased RNA and DNA syntheses; (b) morphological features that are compatible with less primitive leukemia cells; (c) diminished plating efficiency in agar; and (d) loss of their malignancy as determined by the capacity of K-562 cells to develop myelosarcomas in lasat mice. The cytochemical pattern and antigenic markers of the leukemic cells were not modified by treatment with DMSO. These results suggest that the effect of DMSO on K-562 cells is consistent with cytotoxicity rather than a stimulation of cell differentiation.

Human spleen inhibitor of leukaemic cell growth

En este trabajo se describe la purificación de un inhibidor de la síntesis de ARN que afecta secundariamente la síntesis de ADN, y actividad mitótica. El factor ha sido aislado de ocho bazos humanos, comprendiendo dos de enfermos con leucemia mielocítica crónica (LMC) sanas, en los cuales se efectuó la esplenectomía por ruptura traumática del bazo El inhibidor esplénico posee fuerte citotoxicidad sobre células en cultivo provenientes de enfermos con LMC. Estas células tienen el cromosoma de Philadelphia. El inhibidor esplénico tiene un peso molecular de alrededor de 1,000 y es probablaemente un péptido o glicopéptido.