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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
Author(s) -
Cuneo Antonio,
De Angeli Cristiano,
Grazia Roberti Maria,
Piva Nadia,
Bigoni Renato,
Gan dini Domenica,
Matteo Rigolin Gian,
Moretti Sabrina,
Cavaz zini Pierluigi,
Del Senno Laura,
C ASTOLDI GIANLUIGI
Publication year - 1996
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1996.d01-1505.x
Subject(s) - biology , exon , chronic lymphocytic leukemia , fluorescence in situ hybridization , missense mutation , microbiology and biotechnology , mutation , ighv@ , pathology , leukemia , cancer research , immunology , genetics , chromosome , gene , medicine
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.