Phorbol ester induction of early response gene expression in lymphocytic leukemia and normal human B-cells

The spectrum of early response genes induced following phorbol ester (phorbol 12-myristate 13-acetate-PMA) stimulation of B-chronic lymphocytic leukemia cells was compared with that in normal tonsillar B-cells by using a panel of 20 gene probes. Of these, 2 (fos-B and Fra-1) were not expressed in either cell type; 11 displayed a comparable pattern and magnitude of induction in both the cell types, and one anonymous gene (5L3) that was inducible in leukemic cells was not detectably expressed in normal B-cells. Four further anonymous cDNAs (1R21, 10A, 1R19 and 3L11) detected transcripts that were constitutively expressed in normal B-cells with a concomitant reduction in inducibility compared with leukemic B-cells, whilst jun-B and jun-D, which were both inducible in normal B-cells, were constitutively expressed and only marginally PMA-inducible in leukemic B-cells. These data demonstrate clear differences in the PMA-activated early response gene regulatory pathways between normal and lymphocytic leukemia B-cells, which may reflect perturbations in signal transduction pathways that manifest in the differentiation arrest characteristic of these malignant B-cells.