De Novo CD5+ Diffuse Large B-Cell Lymphomas Express VH Genes With Somatic Mutation

Abstract

To clarify the cellular origin of de novo CD5+ diffuse large B-cell lymphoma (CD5+ DLBL), particularly in comparison with other CD5+ B-cell neoplasms such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), we analyzed the nucleotide sequence of the Ig heavy chain variable region (IgVH) genes of de novo CD5+ DLBL cases. All 4 cases examined had extensive somatic mutations in contrast with CLL or MCL. The VH gene sequences of de novo CD5+ DLBL displayed 86.9% to 95.2% homology with the corresponding germlines, whereas those of simultaneously analyzed CLL and MCL displayed 97.6% to 100% homology. The VH family used was VH3 in 1 case, VH4 in 2 cases, and VH5 in 1 case. In 2 of 4 examined cases, the distribution of replacement and silent mutations over the complementarity determining region and framework region in the VH genes was compatible with the pattern resulting from the antigen selection. Clinically, CD5+DLBL frequently involved a variety of extranodal sites (12/13) and lymph node (11/13). Immunophenotypically, CD5+ DLBL scarcely expressed CD21 and CD23 (3/13 and 2/13, respectively). These findings indicate that de novo CD5+ DLBL cells are derived from a B-1 subset distinct from those of CLL or MCL.

De novo CD5‐positive diffuse large B‐cell lymphoma: clinical characteristics and therapeutic outcome

“…In a previous study we demonstrated that CD5 was expressed on the tumour cells in 13/133 patients with DLBL who were consecutively examined in our institutions (Taniguchi et al, 1998). This frequency was consistent with the results reported from Western countries (Burns et al, 1983;Delia et al, 1986).…”

“…Matolcsy et al (1995) reported that a certain number of CD5-positive DLBLs evolved de novo, not as a result of transformation, and that these de novo CD5-positive DLBLs may be distinct from DLBLs with Richter's syndrome, because bcl-6 gene rearrangement was observed in 44% of the de novo cases but not in any Richter's cases. The lack of CD23 also suggests that these CD5-positive DLBLs do not represent a transformation from CLL (Matolcsy et al, 1995;Taniguchi et al, 1998). In addition, the lack of bcl-1 gene rearrangement and cyclin D1 expression suggests that these cases do not represent the blastic variant of MCL (Oka et al, 1994;Matolcsy et al, 1995;Yatabe et al, 1996).…”

CD5 expression correlates with inferior survival and enhances the negative effect of p53 overexpression in diffuse large B‐cell lymphoma

“…15,23,24 It is well known that CD5+ DLBCL has different phenotypes and genotypes from CD5− DLBCL. 25,26 In some literatures, the clinical characteristics of CD5+ DLBCL resemble activated B-cell-like (ABC) DLBCL, and the gene profiling analysis has shown some similar gene expression patterns. 27,28 However, these data are heterogeneous, and no common genetic aberrations have been found.…”

Aggressive B‐cell lymphomas: a review based on the workshop of the XI Meeting of the European Association for Haematopathology

“…The existence of de novo CD5+ diffuse large B-cell lymphomas (DLBCL) has been recently proposed. [8][9][10][11][12][13][14] The importance of its recognition is at least in part its distinction from the pleomorphic or blastoid variants of MCL. [15][16][17][18] Diffuse large B-cell lymphoma DLBCL represents a group of tumours which are heterogeneous on morphological, phenotypic, molecular, and clinical grounds.…”