Chronic lymphocytic leukemia B cells of more than 1% of patients express virtually identical immunoglobulins

We examined the immunoglobulin (Ig) heavy chain variable region genes (VH genes) used by leukemia cells of 1220 unrelated patients with chronic lymphocytic leukemia (CLL). We found 1188 (97%) expressed Ig encoded by a single Ig VH subgroup, the most common of which was VH3 (571 or 48.1%), followed b...

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Bibliographic Details
Published in:Blood 2004-10, Vol.104 (8), p.2499-2504
Main Authors: Widhopf, George F., Rassenti, Laura Z., Toy, Traci L., Gribben, John G., Wierda, William G., Kipps, Thomas J.
Format: Article
Language:English
Subjects:
Alleles
Amino Acid Motifs
Amino Acid Sequence
Base Sequence
Biological and medical sciences
Complementarity Determining Regions - chemistry
Complementarity Determining Regions - genetics
Genes, Immunoglobulin - genetics
Hematologic and hematopoietic diseases
Humans
Immunoglobulins - chemistry
Immunoglobulins - genetics
Leukemia, Lymphocytic, Chronic, B-Cell - genetics
Leukemia, Lymphocytic, Chronic, B-Cell - immunology
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Medical sciences
Molecular Sequence Data
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Summary:We examined the immunoglobulin (Ig) heavy chain variable region genes (VH genes) used by leukemia cells of 1220 unrelated patients with chronic lymphocytic leukemia (CLL). We found 1188 (97%) expressed Ig encoded by a single Ig VH subgroup, the most common of which was VH3 (571 or 48.1%), followed by VH1 (319 or 26.8%) and VH4 (241 or 20.2%). Using allele-specific primers, we found 13.8% of all samples (n = 164) used one major VH1-69 allele, designated 51p1, 163 of which were not somatically mutated. For these cases, there was marked restriction in the structure of the Ig third complementarity determining regions (CDR3s), which were encoded by a small number of unmutated D and JH gene segments. Strikingly, 15 of the 163 cases had virtually identical CDR3s encoded by the second reading frame of D3-16 and JH3. Further analysis revealed that each of these 15 samples used the same unmutated Ig kappa light-chain gene, namely A27. These data reveal that approximately 1.3% (15/1220) of all patients had leukemia cells that expressed virtually identical Ig. This finding provides compelling evidence that the Ig expressed by CLL B cells are highly selected and not representative of the Ig expressed by naive B cells.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2004-03-0818