CD44 activation in mature B-cell malignancies by a novel recurrent IGH translocation

Abstract

Using inverse polymerase chain reaction, we identified CD44, located on chromosome 11p13, as a novel translocation partner of IGH in 9 of 114 cases of gastric, nongastric extranodal, follicular, and nodal diffuse large B-cell lymphoma (DLBCL). Notably, these translocations involving IGHSμ were detected in follicular lymphomas and exclusively in germinal center B cell - like (GCB) - DLBCLs. CD44 is not expressed in reactive GC B cells. The IGHSμ/CD44 translocations substitute Sμ for the CD44 promoter and remove exon 1 of CD44, resulting in the overexpression of Iμ-CD44 hybrid mRNA transcripts activated from derivative 11 that encode a new CD44 variant lacking the leader peptide and with a unique C-terminus (CD44ΔEx1). When overexpressed in vitro in the CD44 - GCB-DLBCL cell line BJAB, CD44ΔEx1 - green fluorescent protein localized to the cytoplasm and nucleus, whereas CD44s - green fluorescent protein (standard form) localized to the plasma membrane. The ectopic expression of CD44ΔEx1 in BJAB cells enhanced their proliferation rate and clonogenic ability, indicating a possible pathogenic role of the translocation. © 2010 by The American Society of Hematology.