title: Richter's syndrome in a case of atypical chronic lymphocytic leukaemia with the t(11;14)(q13;q32): role for a p53 exon 7 gene mutation.
abstract: Clinicobiological, histological, cytogenetic and molecular genetic studies were performed in a case of atypical B-cell chronic lymphocytic leukaemia (B-CLL) with the t(11;14)(q13;q32) evolving into Richter's syndrome (RS) in order (a) to determine the clonal relationship between the cell of origin for B-CLL and RS, and (b) to analyse genetic events underlying the disease progression in this patient. After 4 years following diagnosis, a rapid deterioration of the clinical picture occurred, concomitant with the appearance of large lymphoid blasts in peripheral blood (PB), bone marrow (BM) and ascites samples. A diagnosis of RS was made and cytogenetic analysis revealed karyotype evolution with trisomy 7 and del(17p) in addition to t(11;14). Fluorescence in situ hybridization showed 78% lymphoid blast cells obtained from ascites sample to be trisomic using a chromosome-7-specific pericentromeric probe. Whereas no rearrangement of the c-myc proto-oncogene was detected at disease progression, direct sequencing of p53 gene exon 5-9 revealed an exon 7 missense point mutation. This abnormality was not present in the CLL phase. Immunological staining with the monoclonal antibody PAb-1801, detecting the p53 protein product, revealed a negative pattern in the CLL phase, whereas 24% positivity was documented in representative samples obtained at RS. It is concluded that RS was cytogenetically related with B-CLL in this patient, suggesting the occurrence of a bona fide transformation and that the mutation of p53 exon 7, in association with the development of 17p deletion, possibly played a role in the development of RS.
authors.affiliation: Institute of Haematology, University of Ferrara, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cuneo
authors.forename: C
authors.initials: C
authors.lastname: de Angeli
authors.forename: M G
authors.initials: MG
authors.lastname: Roberti
authors.forename: N
authors.initials: N
authors.lastname: Piva
authors.forename: R
authors.initials: R
authors.lastname: Bigoni
authors.forename: D
authors.initials: D
authors.lastname: Gandini
authors.forename: G M
authors.initials: GM
authors.lastname: Rigolin
authors.forename: S
authors.initials: S
authors.lastname: Moretti
authors.forename: P
authors.initials: P
authors.lastname: Cavazzini
authors.forename: L
authors.initials: L
authors.lastname: del Senno
authors.forename: G
authors.initials: G
authors.lastname: Castoldi
mesh_terms: D000368:Aged; D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11; D002883:Chromosomes, Human, Pair 14; D017931:DNA Primers / Q000235:genetics; D005091:Exons; D005260:Female; D017353:Gene Deletion; D016158:Genes, p53; D006801:Humans; D015448:Leukemia, B-Cell / Q000235:genetics* / Q000276:immunology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D014178:Translocation, Genetic; D014314:Trisomy
chemical_list: D017931:DNA Primers; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas