p53 EXPRESSION IN HAEMATOLOGICAL MALIGNANCIES: RESPONSE TO ALKYLATING AGENT IN THE COMET ASSAY

Aims. The P53 gene is a tumour suppressor, often inactivated by deletion and/or point mutation in malignancies. The incidence of p53 mutation in haematological malignancies varies with malignancy type and cell lineage affected. It is associated with disease progression, poor prognosis and resistance to chemotherapy. The wild-type p53 protein has a short half-life and cannot be detected by immunocytochemistry, whereas the mutated form has an extended half-life and can be. Materials and methods. Using lymphocyte cytospin preparations from patients with a range of haematological malignancies, p53 mutation was assessed with immunocytochemistry. Results. 83 patients showed intracellular p53 in 16 cases, including 4/18 (22%) Non-Hodgkin’s lymphoma (NHL), 3/15 (20%) chronic lymphocytic leukaemia (CLL), 2/13 (15%) myeloma, 2/19 (11%) chronic myeloid leukaemia (CML), 1/3 (33%) hairy cell leukaemia (HCL), 4/15 (27%) myelodysplatic syndromes (MDS) including two transformed acute myeloid leukaemia (AML). Using the Comet assay, lymphocytes from the p53 positive NHL, CLL, CML and AML cases showed reduced damage to the alkylating agent, ethyl methanesulfonate (EMS), when compared to p53 negative cases. Conclusions. This suggested that mutant p53 positive cases are resistant to damage by cytotoxic agents.