Molecular and cytogenetic characterization of expanded B-cell clones from multiclonal versus monoclonal B-cell chronic lymphoproliferative disorders.
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. The expansion of two or more B-cell clones has frequently been reported in individuals with these conditions; potentially, such coexisting clones have a greater probability of interaction with common immunological determinants. Here, we analyzed the B-cell receptor repertoire and molecular profile, as well as the phenotypic, cytogenetic and hematologic features, of 228 chronic lymphocytic leukemia-like and non-chronic lymphocytic leukemia-like clones comparing 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 mono clonal cases, in association with unique hematologic (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.
orfao@usal.es.
Ana
A
Henriques
Arancha
A
Rodríguez-Caballero
Ignacio
I
Criado
Anton W
AW
Langerak
Wendy G
WG
Nieto
Quentin
Q
Lécrevisse
Marcos
M
González
Emília
E
Cortesão
Artur
A
Paiva
Julia
J
Almeida
Alberto
A
Orfao
D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D060965:Clonal Evolution / Q000235:genetics*; D022801:Complementarity Determining Regions / Q000235:genetics; D020732:Cytogenetic Analysis; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D008218:Lymphocytosis / Q000235:genetics* / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000473:pathology; D010802:Phylogeny; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism
D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D011947:Receptors, Antigen, B-Cell