title: p53 gene inactivation in acute lymphoblastic leukemia of B cell lineage associates with chromosomal breakpoints at 11q23 and 8q24.
abstract: The clinical heterogeneity of acute lymphoblastic leukemia (ALL) of B cell lineage reflects the presence of distinct molecular pathways leading to well-defined ALL molecular subtypes. These molecular pathways include the formation of the fusion transcripts BCR/ABL and E2A/PBX1, due to t(9;22) and t(1;19), respectively, as well as rearrangements of the MLL gene at 11q23 and of c-MYC at 8q24. Hyperdiploid ALL in the absence of chromosomal structural abnormalities is an additional ALL molecular subtype. Mutations of the RAS family genes and of the p53 tumor suppressor gene represent additional genetic lesions detected in a fraction (10-20%) of ALL cases. RAS activation in ALL may be detected in all molecular subtypes of ALL and denotes poor prognosis. Conversely, little is known regarding the clinical and biological features of ALL cases carrying p53 mutations. In order to help clarify the role of p53 inactivation in ALL development, we have determined the frequency of p53 mutations throughout the molecular spectrum of B cell lineage ALL. We report that p53 inactivation in ALL of B cell lineage is restricted to cases carrying a rearrangement of MLL or c-MYC, whereas it is consistently negative in other molecular subgroups. These data underline the molecular heterogeneity of ALL of B cell lineage and indicate that at least some of the molecular pathways involved in ALL pathogenesis require more than one genetic lesion.
authors.affiliation: Dipartimento di Scienze Biomediche e Oncologia Umana, Ospedale San Luigi Gonzaga, Torino, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Lanza
authors.forename: G
authors.initials: G
authors.lastname: Gaidano
authors.forename: G
authors.initials: G
authors.lastname: Cimino
authors.forename: F
authors.initials: F
authors.lastname: Lo Coco
authors.forename: G
authors.initials: G
authors.lastname: Basso
authors.forename: L
authors.initials: L
authors.lastname: Sainati
authors.forename: C
authors.initials: C
authors.lastname: Pastore
authors.forename: J
authors.initials: J
authors.lastname: Nomdedeu
authors.forename: G
authors.initials: G
authors.lastname: Volpe
authors.forename: G
authors.initials: G
authors.lastname: Parvis
mesh_terms: D001483:Base Sequence; D001853:Bone Marrow / Q000473:pathology; D002051:Burkitt Lymphoma / Q000097:blood / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002898:Chromosomes, Human, Pair 8; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D005091:Exons; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D015321:Gene Rearrangement; D016259:Genes, myc; D016158:Genes, p53; D011905:Genes, ras; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D051788:Myeloid-Lymphoid Leukemia Protein; D016133:Polymerase Chain Reaction; D011519:Proto-Oncogenes; D014157:Transcription Factors; D014178:Translocation, Genetic
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; D016044:Fusion Proteins, bcr-abl