Peter C. Nowell̀

It is proposed that most neoplasms arise from a single cell of origin, and tumor progression results from acquired genetic variability within the original clone allowing sequential selection of more aggressive sublines. Tumor cell populations are apparently more genetically unstable than normal cells, perhaps from activation of specific gene loci in the neoplasm, continued presence of carcinogen, or even nutritional deficiencies within the tumor. The acquired genetic insta0ility and associated selection process, most readily recognized cytogenetically, results in advanced human malignancies being highly individual karyotypically and biologically. Hence, each patient's cancer may require individual specific therapy, and even this may be thwarted by emergence of a genetically variant subline resistant to the treatment. More research should be directed toward understanding and controlling the evolutionary process in tumors before it reaches the late stage usually seen in clinical cancer.

From an acute B-cell leukemia cell line, a DNA probe was obtained that was specific for chromosome 18 and flanked the heavy chain joining region of the immunoglobulin heavy chain locus on chromosome 14. This probe detected rearrangement of the homologous DNA segment in the leukemic cells and in follicular lymphoma cells with the t(14:18) chromosome translocation but not in other neoplastic or normal B or T cells. The probe appears to identify bcl-2, a gene locus on chromosome 18 (band q21) that is unrelated to known oncogenes and may be important in the pathogenesis of B-cell neoplasms with this translocation.

Summary Possible factors responsible for the initiation of mitotic activity in “gradient” cultures of leukocytes from normal human blood were investigated. Variations of temperature, pH, oxygen tension, carbon dioxide tension, plasma and cell concentrations, as well as the amount of agitation, over at least as wide a range as might be encountered in vivo , produced only moderate quantitative changes in mitotic activity. The mucoprotein plant extract, phytohemagglutinin (PHA), employed originally as a means of separating the leukocytes from whole blood in preparing the cultures, was found to be a specific initiator of mitotic activity: in its presence, cell division occurred; in its absence, no mitoses appeared. The studies suggest that the mitogenic action of PHA does not involve mitosis per se but rather the stage preceding mitosis—the alteration of circulating monocytes and large lymphocytes to a state wherein they are capable of division. The relationship of this mitogenic action of PHA to mitotic and premitotic processes in the body remains to be investigated.