Citations 2
High-level ROR1 associates with accelerated disease progression in chronic lymphocytic leukemia
Cui, Bing , Ghia, Emanuela M. , Chen, Liguang , Rassenti, Laura Z., DeBoever, Christopher , Widhopf, George F., Yu, Jian , Neuberg, Donna , Wierda, William G. , Kanti, R. , Brown, Jennifer R. , Jones, Jeffrey A. , Frazer, Kelly A. , Neuberg, Donna S , Rai, Kanti R , Kay, Neil E , Frazer, Kelly A , Wierda, William G. , Kay, Neil E. , Gribben, John G. , Kipps, Thomas J.
Blood | November 4, 2016 | Volume: 128 | Issue: 25 | Pages: 2931-2940
Key Points The expression level of ROR1 on CLL cells varies between patients. High-level CLL-cell expression of ROR1 associates with more aggressive disease.
Use of IGHV3–21 in chronic lymphocytic leukemia is associated with high-risk disease and reflects antigen-driven, post–germinal center leukemogenic selection
Jain, Sonia , Widhopf, George F., Rassenti, Laura Z., Keating, Michael J. , Wierda, William G. , Brown, Jennifer R. , Rai, Kanti R., Byrd, John C. , Greaves, Andrew, Byrd, John C. , Ghia, Emanuela M. , Gribben, John G. , Rai, Kanti R., Kay, Neil E. , Kipps, Thomas J. , Byrd, John C
Blood | March 8, 2008 | Volume: 111 | Issue: 10 | Pages: 5101-5108
AbstractWe examined the chronic lymphocytic leukemia (CLL) cells of 2457 patients evaluated by the CLL Research Consortium (CRC) and found that 63 (2.6%) expressed immunoglobulin (Ig) encoded by the Ig heavy-chain-variable-region gene (IGHV), IGHV3-21. We identified the amino acid sequence DANGMDV (motif-1) or DPSFYSSSWTLFDY (motif-2) in the Ig heavy-chain (IgH) third complementarity-determining region (HCDR3) of IgH, respectively, used by 25 or 3 cases. The IgH with HCDR3 motif-1 or motif-2, respectively, was paired with Ig light chains (IgL) encoded by IGLV3-21 or IGKV3-20, suggesting that these Ig had been selected for binding to conventional antigen(s). Cases that had HCDR3 motif-1 had a median time from diagnosis to initial therapy comparable with that of cases without a defined HCDR3 motif, as did cases that used mutated IGHV3-21 (n = 27) versus unmutated IGHV3-21 (n = 30). Of 7 examined cases that used Ig encoded by IGHV3-21/IGLV3-21, we found that 5 had a functionally rearranged IGKV allele that apparently had incurred antigendriven somatic mutations and subsequent rearrangement with KDE. This study reveals that CLL cells expressing IGHV3-21/IGLV3-21 most likely were derived from B cells that had experienced somatic mutation and germinal-center maturation in an apparent antigen-driven immune response before undergoing Ig-receptor editing and after germinal-center leukemogenic selection.