POTENTIAL ROLE FOR WILD-TYPE P53 IN LEUKEMIAS WITH MLL GENE TRANSLOCATIONS

We used single-strand conformation polymorphism (SSCP) analysis of p53 exons 4-8 to screen for possible mutations in 25 pediatric de novo le ukemias with translocations of the MLL gene at chromosome band 11q23, Of the 25 patients, 21 were infants. Fifteen cases were acute myeloid leukemia (AML), eight were acute lymphoblastic leukemia (ALL), and two cases were biphenotypic, Nineteen cases were studied at diagnosis and six at time of relapse, p53 mutations were absent in all 19 cases stu died at the time of diagnosis. The only mutation was a TGC-->TTC trans version (cys-->phe) at codon 141 in exon 5 in a case of infant ALL at relapse that occurred by subclone evolution after MLL gene translocati on, We previously showed that p53 mutations are also absent in pediatr ic treatment-related leukemias with MLL gene translocations. The absen ce of p53 mutations at initial transformation may suggest that the ant i-apoptotic effect of mutant p53 is not important in leukemias with ML L gene translocations. Alternatively, exogenous DNA damage may be the common feature in treatment-related and de novo cases. Since MLL gene translocations may occur through DNA repair and wild-type p53 is centr al to DNA repair, the absence of p53 mutations raises the possibility that wild-type p53, not mutant p53, may be important in the genesis of leukemias with these translocations.