FREQUENT P53 OVEREXPRESSION IN THERAPY-RELATED MYELODYSPLASTIC SYNDROMES AND ACUTE MYELOID LEUKEMIAS - AN IMMUNOHISTOCHEMICAL STUDY OF BONE-MARROW BIOPSIES

p53 overexpression was studied immunohistochemically in paraffin-embed ded bone marrow biopsies using a recently described technique for anti gen retrieval based on microwave oven heating of paraffin sections. Us ing a monoclonal antibody (PAb1801) that reacts with human cellular p5 3, nuclear staining was detected in 7/11 (63%) therapy-related myelody splastic syndromes and in 3/ 4 (75%) therapy-related acute myeloid leu kemias. Conversely, staining for p53 was seen only in 9/40 (22%) cases of ''primary'' hematologic conditions (P < 0.007); these included mye lodysplastic syndromes [#2], acute myeloid leukemia [#4], and chronic granulocytic leukemia in accelerated phase or blast crisis [#3]. Biops ies of normal controls and of chronic granulocytic leukemia in stable phase were consistently p53(-). Nine of the 10 karyotyped p53(+) acute myeloid leukemia/myelodysplastic syndrome cases showed complex cytoge netic findings with frequent involvement of chromosome 5 and/or 7. Onl y four of the 33 karyotyped p53(-) cases showed similar cytogenetic ch anges. Chromosome 17 involvement was present in four of 13 (31%) cytog enetically assessed p53+ cases, but in none of the p53(-). In univaria te analysis, p53 expression in both MDS and AML was significantly asso ciated with shorter survival. The frequent overexpression of p53 in th erapy-related myelodysplastic syndromes, therapy-related acute myeloid leukemias and in accelerated phase/blast crisis, chronic granulocytic leukemia and its strong association with complex karyotypes suggests an important role of this gene in the pathogenesis of these leukemic c onditions.