BCL-1 rearrangements and p53 mutations in atypical chronic lymphocytic leukemia with t(11;14)(q13;q32)

Background and Objectives. The translocation t(11;14) (q13;q32), typically described in mantle cell lymphomas (MCL), has also been found in some cases of non-MCL lymphoproliferative disorders, such as splenic lymphoma with vi llous lymphocytes (SLVL), multiple myeloma (MM), prolymphocytic leukemia (P LL), typical and atypical chronic lymphocytic leukemia (CLL and aCLL). In o rder to define better the genetic features of aCLL with t(11;14), which cou ld represent a distinct disease subset, we looked for genetic lesions in th e BCL-1 locus and in BCL-2, BCL-6, c-myc and p53 genes. Design and Methods. We investigated a panel of B-lymphoproliferative disord ers with translocation t(11;14)(q13;q32) including nine aCLL, six MCL and o ne MM. Southern and Northern blot analyses were used to investigate DNA str ucture and RNA expression; SSCP and direct sequencing were used to detect a nd characterize p53 point mutations; cytofluorimetric analysis was used to quantify p53 protein. Results. Alterations of BCL-2, BCL-6 and c-myc were not detected. Conversel y, BCL-1 rearrangements were present in 4 out of 7 aCLL and in 2 out of 4 M CL. A high incidence of p53 gene alterations was found, almost equivalent i n aCLL and MCL. Interpretation and Conclusions. Our results indicate that the occurrence of BCL-1 locus lesions in aCLL selected for t(11;14) is as high as in MCL. In terestingly, rearrangements in the mTC1 (minor translocation cluster 1) wer e only found in aCLL. Therefore, the two B-cell chronic lymphoproliferative disorders share similar molecular rearrangements and the t(11;14) identifi es a subset of B-CLL sharing molecular features with MCL and characterized by aggressive clinical evolution. (C) 2000, Ferrata Storti Foundation.