The Control of Proliferation, Survival and Apoptosis in Human Multiple Myeloma Cells in vitro

Abstract

The biology of human multiple myeloma (MM) was poorly understood until recently. Only when IL-6 had been identified as an important growth factor for MM cells has it been possible to establish cell lines and to maintain fresh MM biopsy cells in vitro for weeks-months (Kawano et al 1988, Klein et al 1990, Nilsson et al 1990). This has allowed controlled in vitro studies of various aspects of the genotype and phenotype of MM cells during the 1990s. Some features are characteristic for MM cells. They include a restriction of the growth of MM cells almost exclusively to the bone marrow, chromosomal heterogeneity within and between individual MM clones, genetic instability, the presence at a high frequency of a translocation to the immunoglobulin (Ig) heavy chain or Ig light chain locus, a high and deregulated expression of c-Myc, a high expression of Bcl-2 and often a dependence of IL-6 and/or IGF-I as growth and survival factors. A common characteristic of MM cells both in vitro and in vivo is also that they proliferate slowly. At the population level the doubling time is often several days as a result of a long generation time (usually exceeding 36 hrs) and a high apoptotic rate. The first MM cell line established in our laboratory was in 1970 (Nilsson et al 1970). During the following decades additional MM lines were established (Nilsson, 1992) and a selected panel of lines, consisting also of MM cell lines established elsewhere, have been instrumental in studies on the control of growth and apoptosis during the last few years.