Chronic lymphocytic leukemia preceded by cold agglutinin disease: intraclonal immunoglobulin light-chain diversity in V(H)4-34 expressing single leukemic B cells.
Autoimmune phenomena may precede or accompany lymphoid malignancies, especially B-chronic lymphocytic leukemia (B-CLL). We report a patient with a 7-year history of primary (idiopathic) cold agglutinin (CA) disease in whom B-CLL subsequently developed. Immunophenotyping and single-cell reverse transcription-polymerase chain reaction (RT-PCR) were applied to investigate the origin and diversification of leukemic B cells. The obtained data indicate a memory cell-type origin of the B-CLL cells. Remarkably, the IgV(kappa) genes of the B-CLL cells showed intraclonal diversity, whereas the mutational pattern of their paired IgV(H) genes were invariant. Thus, the light-chain-restricted intraclonal diversity in individual leukemic B cells in this patient strongly indicates a differential regulation or selection of the ongoing mutational process. Of note, our findings suggest that this B-CLL had developed from the patient's CA-producing B-cell population.
Ruzickova
Sarka
S
Deutsches Rheumaforschungszentrum, Berlin, Germany.
Pruss
Axel
A
Odendahl
Marcus
M
Wolbart
Karsten
K
Burmester
Gerd-Rüdiger
GR
Scholze
Jürgen
J
Dörner
Thomas
T
Hansen
Arne
A
D000744:Anemia, Hemolytic, Autoimmune / Q000235:genetics / Q000473:pathology*; D001402:B-Lymphocytes / Q000737:chemistry / Q000473:pathology*; D001483:Base Sequence; D002999:Clone Cells / Q000473:pathology; D018076:DNA, Complementary / Q000235:genetics; D018450:Disease Progression; D005500:Follow-Up Studies; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007075:Immunoglobulin M / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D007156:Immunologic Memory; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010266:Paraproteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid
D018076:DNA, Complementary; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D010266:Paraproteins