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Blood, 1 November 2002, Vol. 100, No. 9, pp. 3419-3422

BRIEF REPORT

Chronic lymphocytic leukemia preceded by cold agglutinin disease: intraclonal immunoglobulin light-chain diversity in VH4-34 expressing single leukemic B cells

Sarka Ruzickova, Axel Pruss, Marcus Odendahl, Karsten Wolbart, Gerd-Rüdiger Burmester, Jürgen Scholze, Thomas Dörner, and Arne Hansen

From Deutsches Rheumaforschungszentrum, Berlin; Department of Transfusion Medicine/Outpatients Department and Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany.

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 IgVkappa genes of the B-CLL cells showed intraclonal diversity, whereas the mutational pattern of their paired IgVH 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.

© 2002 by The American Society of Hematology.
 

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