Molecular and cytogenetic characterization of expanded B-cell clones from multiclonal versus monoclonal B-cell chronic lymphoproliferative disorders.

Henriques, A; Rodriguez-Caballero, A; Criado, I; Langerak, AW; Nieto, WG; Lecrevisse, Q; Gonzáles, M; Cortesão, E; Paiva, A; Almeida, J; Orfão, A

http://hdl.handle.net/10400.4/1645

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Authors

Henriques, A

Rodriguez-Caballero, A

Abstract(s)

Chronic antigen-stimulation has been recurrently involved in the earlier stages of monoclonal B-cell lymphocytosis, chronic lymphocytic leukemia and other B-cell chronic lymphoproliferative disorders. Among these individuals, expansion of ≥2 B-cell clones has been frequently reported; potentially, such coexisting clones have a greater probability of interaction with common immunological determinants. Here, we comparatively analyzed the B-cell receptor repertoire and the molecular profile, as well as the phenotypic, cytogenetic and hematological features of 228 chronic lymphocytic leukemia-like and non-chronic lymphocytic leukemia-like clones between multiclonal (n=85 clones from 41 cases) versus monoclonal (n=143 clones) monoclonal B-cell lymphocytosis, chronic lymphocytic leukemia and other B-cell chronic lymphoproliferative disorders. The B-cell receptor of B-cell clones from multiclonal cases showed a slightly higher degree of HCDR3 homology than B-cell clones from monoclonal cases, in association with unique hematological (e.g. lower B-lymphocyte counts) and cytogenetic (e.g. lower frequency of cytogenetically altered clones) features usually related to earlier stages of the disease. Moreover, a subgroup of coexisting B-cell clones from individual multiclonal cases which were found to be phylogenetically related, showed unique molecular and cytogenetic features: they more frequently shared IGHV3 gene usage, shorter HCDR3 sequences with a greater proportion of IGHV mutations and del(13q14.3), than other unrelated B-cell clones. These results would support the antigen-driven nature of such multiclonal B-cell expansions, with potential involvement of multiple antigens/epitopes.