Biased Immunoglobulin VH Recombination and Increased Expression of Chemokine Receptor XCR1 Are Distinct Features of Bone Marrow-Derived Diffuse Large B-Cell Lymphoma
Y Yamashita, D Kajiura, S Nakamura, S Toyokuni, N Mori. Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan; Nagoya University Hospital, Nagoya, Aichi, Japan
Background: Bone marrow-derived diffuse large B-cell lymphoma (DLBCL) presents a poor prognosis, often associated with hemophagocytic syndrome, and shares the pathologic entity with Asian-variant intravascular large B-cell lymphoma (IVL) in which bone marrow involvement is observed in 75% of the cases. However, immunohistochemical marker molecules distinguishing these entities from nodal DLBCL are not established.
Design: PCR and sequence analyses of the immunoglobulin VH gene were performed in 14 patients of bone marrow-derived DLBCL to evaluate the VH family usage and differentiation status of the neoplastic B-cells. Oligonucleotide microarray restricted to the expression of chemokines and chemokine receptors were performed in comparison of 4 samples of bone marrow-derived DLBCL with 8 samples of control nodal DLBCL. Statistical analyses were performed by the Mann-Whitney U Test. Immunohistochemical analyses were performed in 25 cases of bone marrow-derived DLBCL and 23 cases of control nodal DLBCL.
Results: Eleven of the 14 cases had VH recombinations previously reported to encode autoreactive antibodies, with 5 cases of VH3-7 and 3 cases of VH4-34. Others included 3-23, 3-48 and 4-39. Somatic hypermutation was detected in all the 14 cases, suggesting the post-germinal center status of the neoplastic B-cells. Chemokine/chemokine receptor microarray revealed that chemokine receptor XCR1 was significantly overexpressed (p<0.05) in the cases of bone marrow-derived DLBCL, which was confirmed by immunohistochemistry in 80% of the cases.
Conclusions: Biased immunoglobulin gene recombination to autoreactive VH families and overexpression of chemokine receptor XCR1 are distinct features of the neoplastic B-cells in bone marrow-derived DLBCL. This suggests a distinct differentiation of the neoplastic B cells between bone marrow-derived DLBCL and nodal DLBCL. Our findings will be helpful for the differential diagnosis of these entities.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 181, Wednesday Morning