Genomic aberrations in chronic lymphocytic leukemia are important independent predictors of disease progression and survival. These findings have implications for the design of risk-adapted treatment strategies.

Immunoglobulin variable heavy chain gene (V H ) mutation status and VDJ rearrangement structure were analyzed in 141 patients with mantle cell lymphoma (MCL) and correlated with biologic and clinical characteristics; 29% of the MCLs displayed mutated V H using a 98% germline homology cutoff. Striking differences occurred in the V H mutation subgroups with respect to the use of specific V genes. Rearrangements involving V4-34 and V3-21 were almost exclusively unmutated, whereas rearrangements using V4-59 and V3-23 were typically mutated. Significant association occurred between mutated V H with shorter CDR3 lengths and the use of J H 4b. V3-21 and V4-59 were involved in highly characteristic rearrangements, implying that antigen specificity might have been involved in MCL development. There was no evidence for isotype switch recombination or Bcl-6 expression in any MCL. ZAP70 expression was not different in V H -mutated or -unmutated MCL. Although the deletions 11q؊ and 17p؊ showed a balanced distribution, an overrepresentation was observed for trisomies ؉3q, ؉8q, and tetraploidy in the V H -unmutated subgroup and ؉12q in the V H -mutated subgroup. Clinically, mutated V H was associated with a higher rate of complete remission, but there was no correlation between V H mutation status and other clinical characteristics or overall survival. (Blood. 2003; 102:3003-3009)