Acute leukemias carrying MLL 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 MLL rearrangements. In order to assess the extent of TP53 inactivation throughout the immunophenotypic 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 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 3/16 cases in other age groups. Overall, our data suggest that (1) TP53 inactivation is a relatively common event in leukemias with MLL rearrangements irrespective 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 conception of the child) corresponding to the development of acute leukemias of infancy.

Lanza, C., Gaidano, G., Cimino, G., Pastore, C., Nomdedeu, J., Volpe, G., et al. (1996). Distribution of TP53 mutations among acute leukemias with MLL rearrangements. GENES, CHROMOSOMES & CANCER, 15(1), 48-53 [10.1002/(SICI)1098-2264(199601)15:1<48::AID-GCC7>3.0.CO;2-4].

Distribution of TP53 mutations among acute leukemias with MLL rearrangements

LO COCO, FRANCESCO;
1996-01-01

Abstract

Acute leukemias carrying MLL 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 MLL rearrangements. In order to assess the extent of TP53 inactivation throughout the immunophenotypic 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 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 3/16 cases in other age groups. Overall, our data suggest that (1) TP53 inactivation is a relatively common event in leukemias with MLL rearrangements irrespective 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 conception of the child) corresponding to the development of acute leukemias of infancy.
gen-1996
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/15 - MALATTIE DEL SANGUE
English
Acute Disease; Adolescent; Base Sequence; Child; DNA; DNA-Binding Proteins; Histone-Lysine N-Methyltransferase; Humans; Infant; Leukemia; Middle Aged; Molecular Sequence Data; Mutation; Myeloid-Lymphoid Leukemia Protein; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Tumor Suppressor Protein p53; Gene Rearrangement; Proto-Oncogenes; Transcription Factors
Lanza, C., Gaidano, G., Cimino, G., Pastore, C., Nomdedeu, J., Volpe, G., et al. (1996). Distribution of TP53 mutations among acute leukemias with MLL rearrangements. GENES, CHROMOSOMES & CANCER, 15(1), 48-53 [10.1002/(SICI)1098-2264(199601)15:1<48::AID-GCC7>3.0.CO;2-4].
Lanza, C; Gaidano, G; Cimino, G; Pastore, C; Nomdedeu, J; Volpe, G; Vivenza, C; Parvis, G; Mazza, U; Basso, G; Madon, E; LO COCO, F; Saglio, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/161720
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