Novel and Uncommon Chromosome Aberrations in Chronic Lymphocytic Leukemia: Cytogenetic, FISH and Clinical Evaluation

Abstract

The identification of the non-random genetic alterations associated with cancer has great importance not only to basic research but also to disease management as diagnostic and prognostic markers. In contrast to other types of lymphomas, translocations are rare events in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and not any CLL/SLL-specific translocation has been found yet. Moreover, translocations have been reported to be a prognostic marker for an unfavorable clinical outcome. The purpose of our study was to contribute to the understanding of the chromosome alterations associated with this group of lymphoid malignancies. The combination of conventional cytogenetics with FISH (fluorescence in situ hybridization) analysis allowed us a more accurate definition of the genomic aberrations involved in CLL/SLL. Novel and uncommon chromosome rearrangements were found in our series. In the present work, we describe the cytogenetic and FISH analyses of 12 CLL/SLL patients out of 150 cases with successful cytogenetic study, that interestingly showed in their karyotypes new or infrequent clonal chromosome rearrangements, all of them associated to adverse clinical course with partial or null response to different chemotherapeutic agents. We identified 16 different chromosome rearrangements and translocations were the most frequent aberration (7/16; 43,8%). Some of these findings were recently reported by us as a new alterations in SLL/CLL patients: t(2;17)(p21;q23); der(17)t(12;17)(q13;q25); der(14)(t(11;14)(q13;q24), t(5;12;19)(q15;p11;q13); psu dic (17;2)(p11.2;p21), psu dic (12;21)(q24;q10), t(10;14)(q22;q32), del(3)(p11) and del(5)(q15). Translocation t(11;13)(p15;q22) and del(18)(p11) were not previously described, meanwhile, dic(17;18)(p11.2;p11.2), dup(12)(q13q24), del(7)(q34), t(2;14)(p11;q32) and del(7)(q11) were infrequently reported in the literature. Translocation t(2;17)(p21;q23) is recurrent in our series and t(2;14)(p11;q32) became recurrent from our data. Chromosomes 17, 2, 12 and 14 were the most frequently involved. Twenty one different breakpoints were found and 38.1% (8/21) of them, such as 2p21, 5q15, 17p11.2, 17q23, 12q13, 12q24, 14q32 and 18p11 were recurrent in our series. All but one patient of our series showed an unfavorable clinical outcome. A detailed analysis and a review of the cytogenetic and molecular cytogenetics findings in CLL/SLL were performed. Our findings may facilitate the understanding of genetic events associated with development and progression of CLL/SLL and may have implications in the clinical management of patients with this disease.