Over 20% of patients with chronic lymphocytic leukemia carry stereotyped receptors: Pathogenetic implications and clinical correlations.
The chronic lymphocytic leukemia (CLL) immunoglobulin repertoire is biased and characterized by the existence of subsets of cases with closely homologous ("stereotyped") complementarity-determining region 3 (CDR3) sequences. In the present series, 201 (21.9%) of 916 patients with CLL expressed IGHV genes that belonged to 1 of 48 different subsets of sequences with stereotyped heavy chain (H) CDR3. Twenty-six subsets comprised 3 or more sequences and were considered "confirmed." The remaining subsets comprised pairs of sequences and were considered "potential"; public database CLL sequences were found to be members of 9 of 22 "potential" subsets, thereby allowing us to consider them also "confirmed." The chance of belonging to a subset exceeded 35% for unmutated or selected IGHV genes (eg, IGHV1-69/3-21/4-39). Comparison to non-CLL public database sequences showed that HCDR3 restriction is "CLL-related." CLL cases with selected stereotyped immunoglobulins (IGs) were also found to share unique biologic and clinical features. In particular, cases expressing stereotyped IGHV4-39/IGKV1-39-1D-39 and IGHV4-34/IGKV2-30 were always IgG-switched. In addition, IGHV4-34/IGKV2-30 patients were younger and followed a strikingly indolent disease, contrasting other patients (eg, those expressing IGHV3-21/IGLV3-21) who experienced an aggressive disease, regardless of IGHV mutations. These findings suggest that a particular antigen-binding site can be critical in determining the clinical features and outcome for at least some CLL patients.
Stamatopoulos
Kostas
K
Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece.
Belessi
Chrysoula
C
Moreno
Carol
C
Boudjograh
Myriam
M
Guida
Giuseppe
G
Smilevska
Tatjana
T
Belhoul
Lynda
L
Stella
Stefania
S
Stavroyianni
Niki
N
Crespo
Marta
M
Hadzidimitriou
Anastasia
A
Sutton
Laurent
L
Bosch
Francesc
F
Laoutaris
Nikolaos
N
Anagnostopoulos
Achilles
A
Montserrat
Emili
E
Fassas
Athanasios
A
Dighiero
Guillaume
G
Caligaris-Cappio
Federico
F
Merle-Béral
Hélène
H
Ghia
Paolo
P
Davi
Frédéric
F
D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000595:Amino Acid Sequence; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D001483:Base Sequence; D015331:Cohort Studies; D000939:Epitopes; D005500:Follow-Up Studies; D005602:France; D005787:Gene Frequency; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006115:Greece; D006801:Humans; D017578:Immunoglobulin Class Switching; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007134:Immunoglobulin Switch Region; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007558:Italy; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000209:etiology / Q000276:immunology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012217:Rheumatoid Factor / Q000276:immunology; D017385:Sequence Homology; D027041:Somatic Hypermutation, Immunoglobulin; D013030:Spain
D000939:Epitopes; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D012217:Rheumatoid Factor; D051997:ADP-ribosyl Cyclase 1