The phenotypic abnormality in leukemia: a defective cell-factor interaction?

Differentiation of hemopoietic cells appears to depend upon specific interactions of certain cell-factors. The phenotypic abnormality in leukemia may involve an impairment in these interactions. In this report we present some of our views of leukemogenesis with respect to cell-factor interaction and the feasibility of experimental approaches to this problem. In culture, the interaction of myelogenous cells with factor(s) leading to differentiation can be measured either with a suspension mass culture method or by a solid (semi-soft) clonal method. The protein factors that support the growth of hemopoietic cells in suspension culture are termed growth stimulating factors (GSA) and in semi-solid culture, colony stimulating factors (CSA). Studies using conditioned medium prepared from phytohemagglutinin stimulated human lymphocytes (PHA-LyCM) and whole human embryo cells (WHE) revealed that GSA and CSA were not identical for growth of either normal human or leukemic leukocytes. In some cases maturation of leukemic leukocytes was observed. Fractionation of PHA-LyCM showed that there are three peaks for CSA. Each peak contains different fractions for supporting cellular proliferation, differentiation, and self-renewal of precursor cells in suspension culture. Apparently, each contains heterogenous species of protein factors some of which functionally overlap, while others do not.