DISTRIBUTION OF TP53 MUTATIONS AMONG ACUTE LEUKEMIAS WITH MLL REARRANGEMENTS

Acute leukemias carrying MLL rearrangements are characterized by a hig h degree of clinical and immunologic heterogeneity, as demonstrated by variability in their immunophenotype, consistent with lymphoid or mye loid/monoblastic derivation, as well as their occurrence in distinct a ge groups from infancy to adulthood. Recently, it was shown that inact ivation of the TP53 tumor suppressor gene occurs frequently in cases o f acute lymphoblastic leukemia carrying MLL rearrangements. In order t o assess the extent of TP53 inactivation throughout the immunophenotyp ic and clinical spectrum of MLL(+) acute leukemias, we tested for TP53 mutations 29 cases of MLL(+) acute leukemias displaying lymphoid (13 cases) or myeloid/monoblastic (16 cases) features and belonging to dif ferent age groups. Mutations were detected in 6/16 myeloid/monoblastic cases and in 3/13 lymphoid cases. Among myeloid/monoblastic leukemias , the TP53 mutations occurred in 3/4 infants, but only in 3/16 cases i n other age groups. Overall, our data suggest that (1) TP53 inactivati on is a relatively common event in leukemias with MLL rearrangements i rrespective of the leukemic phenotype and of the patients' age; (2) at least two genetic lesions (i.e., MLL rearrangement and TP53 mutation) have accumulated in the short time (few weeks after the birth or conc eption of the child) corresponding to the development of acute leukemi as of infancy. (C) 1996 Wiley-Liss, Inc.