Progressive B-cell chronic lymphocytic leukaemia frequently exhibits aberrant p53 expression.
We have analysed the p53 status in non-progressive and progressive chronic B-cell leukemia (B-CLL) by ELISA, immunoprecipitation, FACS and cDNA sequencing in relation to in vitro proliferation in response to Staphylococcus aureus strain Cowan I (SAC) and IL-2. In FACS, cells from progressive leukaemia were found to over-express p53 with a conformation 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 codon 179 His to Gln change in one of the ELISA-positive, progressive B-CLL but failed to reveal any mutations in 4 other ELISA-positive, progressive B-CLL. Among progressive B-CLL populations, 10/14 responded by proliferation in vitro to SAC/IL-2. In non-progressive cells, low levels of p53 were found by FACS, none was positive in the PAb240 ELISA and 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, resting and activated, and in EBV-transformed B-cell lines, in contrast to the high expression observed in Burkitt lymphoma cell lines with verified p53 mutations. We conclude that progressive B-CLL is characterized by aberrant p53 expression which may be a significant prognostic factor.
Aguilar-Santelises
M
M
Microbiology and Tumour Biology Center, Karolinska Institute, Stockholm, Sweden.
Magnusson
K P
KP
Wiman
K G
KG
Mellstedt
H
H
Jondal
M
M
D000328:Adult; D000368:Aged; D001483:Base Sequence; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016158:Genes, p53; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011233:Precipitin Tests