Distribution of TP53 mutations among acute leukemias with MLL rearrangements

✍ Scribed by Carlo Lanza; Gianluca Gaidano; Giuseppe Cimino; Cristina Pastore; Josep Nomdedeu; Gisella Volpe; Claudia Vivenza; Guido Parvis; Umberto Mazza; Giuseppe Basso; Enrico Madon; Francesco Lo Coco; Giuseppe Saglio

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 499 KB
• Volume: 15
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/(sici)1098-2264(199601)15:1<48::aid-gcc7>3.0.co;2-4

✦ Synopsis

Acute leukemias carrying MU rearrangements are characterized by a high degree of clinical and immunologic heterogeneity, as demonstrated by variability in their immunophenotype, consistent with lymphoid or myeloid/monoblastic derivation, as well as their Occurrence in distinct age groups from infancy to adulthood. Recently, it was shown that inactivation of the TP53 tumor suppressor gene occurs frequently in cases of acute lymphoblastic leukemia carrying MU rearrangements. In order t o assess the extent of TP53 inactivation throughout the immunophenotypic and clinical spectrum of M U + acute leukemias, we tested for TP53 mutations 29 cases of MLL+ acute leukemias displaying lymphoid (I 3 cases) o r myeloid/monoblastic (I 6 cases) features and belonging t o different 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/ I6 cases in other age groups. Overall, our data suggest that (I) TP53 inactivation is a relatively common event in leukemias with MU rearrangements irrespective of the leukemic phenotype and of the patients' age;

(2) at least two genetic lesions (i.e., M U rearrangement and TP53 mutation) have accumulated in the short time (few weeks after the birth or conception of the child) corresponding to the development of acute leukemias of infancy. Genes Chromosom Cancer 1548-53 (1996).