Excessive antigen reactivity may underlie the clinical aggressiveness of chronic lymphocytic leukemia stereotyped subset #8.

Abstract

Subset #8 is a distinctive subset of patients with chronic lymphocytic leukemia (CLL) defined by the expression of stereotyped IGHV4-39/IGKV1(D)-39 B-cell receptors. Subset #8 patients experience aggressive disease and exhibit the highest risk for Richter transformation among all CLL. In order to obtain biological insight into this behavior, we profiled the antigen reactivity and signaling capacity of subset #8 vs other clinically aggressive stereotyped subsets, namely subsets #1 and #2. Twenty-seven monoclonal antibodies (mAbs) from subsets #1, #2, and #8 CLL clones were prepared as recombinant human immunoglobulin G1 and used as primary antibodies in enzyme-linked immunosorbent assays against representatives of the major classes of established antigenic targets for CLL. Subset #8 CLL mAbs exhibited broad polyreactivity as they bound to all antigens tested, in clear contrast with the mAbs from the other subsets. Antigen challenge of primary CLL cells indicated that the promiscuous antigen-binding activity of subset #8 mAbs could lead to significant cell activation, again in contrast to the less responsive CLL cells from subsets #1 and #2. These features constitute a distinctive profile for CLL subset #8, supporting the existence of distinct mechanisms of aggressiveness in different immunogenetic subsets of CLL.

• Authors: Maria Gounari, Stavroula Ntoufa, Benedetta Apollonio, Nikos Papakonstantinou, Maurilio Ponzoni, Charles C Chu, Davide Rossi, Gianluca Gaidano, Nicholas Chiorazzi, Kostas Stamatopoulos, Paolo Ghia
• Journal: Blood (Blood) Vol. 125 Issue 23 Pg. 3580-7 (Jun 04 2015) ISSN: 1528-0020 [Electronic] United States
• PMID: 25900981 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by The American Society of Hematology.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Neoplasm
• Antigens, Neoplasm

Topics

• Antibodies, Monoclonal (immunology)
• Antibodies, Neoplasm (immunology)
• Antigens, Neoplasm (immunology)
• Female
• Humans
• Leukemia, Lymphocytic, Chronic, B-Cell (immunology, pathology)
• Male