PROGRESSIVE B-CELL CHRONIC LYMPHOCYTIC-LEUKEMIA FREQUENTLY EXHIBITS ABERRANT P53 EXPRESSION

We have analysed the p53 status in non-progressive and progressive chr onic B-cell leukaemia (B-CLL) by ELISA, immunoprecipitation, FACS and cDNA sequencing in relation to in vitro proliferation in response to S taphylococcus aureus strain Cowan I (SAC) and IL-2. In FACS, cells fro m progressive leukaemia were found to over-express p53 with a conforma tion recognized by PAb240. In a PAb240-based ELISA, 60% of progressive B-CLL were positive. DNA sequencing of p53 exons 5 to 9 revealed a co don 179 His to Gin change in one of the ELISA-positive, progressive B- CLL but failed to reveal any mutations in 4 other ELISA-positive, prog ressive B CLL. Among progressive B-CLL populations, 10/14 responded by proliferation in vitro to SAC/IL-2. In non-progressive cells, low lev els of p53 were found by FACS, none was positive in the PAb240 ELISA a nd only one case showed a weak proliferative response to SAC/IL-2. Low p53 expression was also seen in different types of normal B cells, re sting and activated, and in EBV-transformed B-cell lines, in contrast to the high expression observed in Burkitt lymphoma cell lines with ve rified p53 mutations. We conclude that progressive B-CLL is characteri zed by aberrant P53 expression which may be a significant prognostic f actor. (C) 1994 Wiley-Liss, Inc.