GENETIC-ANALYSIS OF P53 AND RB1 TUMOR-SUPPRESSOR GENES IN BLAST CRISIS OF CHRONIC MYELOID-LEUKEMIA

We have investigated the involvement of the p53 and RB1 tumor-suppress or genes in 26 cases of chronic myeloid leukemia (CML) blast crisis, i ncluding 17 myeloid, eight lymphoid, and one megakaryoblastic crisis. The presence of p53 mutations in exons 5 through 9 was tested by the P CR-single-strand conformation polymorphism (SSCP) assay, followed by P CR-direct sequencing; in addition, loss of heterozygosity (LOH) at 17p 13, the site of the p53 gene, was assayed by Southern blot. Given the variability of the mechanisms of inactivation of the RB1 gene in human tumors, a combination of Southern blot and mutational analysis by PCR -SSCP was used. p53 mutations were restricted to one case of myeloid b last crisis, showing a CGC-->TGC (Arg-->Cys) mutation at codon 283; tw o additional cases displayed LOH at 17p13 in the absence of p53 mutati ons. No molecular lesions of the RB1 gene were detected in any of the cases analyzed. These data indicate that inactivation of p53 and RB1 i s a rare event in the molecular pathogenesis of CML acute transformati on.