Splenic marginal zone lymphoma: Clinical clustering of immunoglobulin heavy chain repertoires

Immunoglobulin gene usage and somatic mutation patterns were studied in 59 patients with splenic marginal zone lymphoma and were correlated with clinical characteristics. Fifty-nine IGHV rearrangements were amplified. IGHV1, IGHV3, and IGHV4 subgroups accounted for 30%, 56%, and 14% of sequences, respectively. IGHV genes most frequently used were IGHV1-2 (n=12), IGHV3-23 (n=15), IGHV3-30 (n=7) and IGHV4-34 (n=5). IGHV was unmutated in 25%. Villous lymphocytes >10% were detected in 50% of patients belonging to the IGHV1-2 group, in 21% of the IGHV3-23 group, and in no patient of the IGHV3-30 group (p=0.05). Liver involvement was present in 50% of the IGHV3-30 group, in 9% of the IGHV3-23 group, and in no patient of the IGHV1-2 group (p=0.04). HCV-serology was positive in 50% of the IGHV3-30 group, in 7% of the IGHV3-23 group, and in 17% of the IGHV1-2 group (p=0.04). The proportion of intermediate and high risk patients according to the SMZL score was higher in the unmutated respect to the mutated group (69% vs 32%, p=0.05). In conclusion, IGHV rearrangement analysis in splenic marginal zone B-cell lymphoma reveals a non-random preference for use of IGHV1-2, IGHV3-23 and IGHV3-30 genes, whose presence differs according to clinical features and prognostic category.