Phorbol ester-induced changes in human leukemic pre-B lines

The genomic analysis of four non-T-leukemic lines NALM-1, KM-3, NALL-1, and NALM-16 shows a rearranged configuration of the immunoglobulin mu chain genes, indicating that they represent early B stages of differentiation. The differentiative potential of these pre-B cell lines was tested using the phorbol ester tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA). Phenotypic changes in the immunological marker profile (induction of BA-1 and BA-2 antigens) are observed, presumably reflecting events occurring in precursor B cells. However, no maturation to immunoglobulin mu chain production could be obtained. The limited maturation can be explained on the basis of possible aberrant mu chain gene rearrangements, or other mechanisms of a regulatory nature, preventing the transcription and/or the translation of rearranged mu chain genes.