Division of chronic lymphocytic leukemia (CLL) into 2 subsets, with and without mutations of the IgVH genes, has important prognostic significance. The unmutated subset, with an inferior prognosis, was originally defined by 98% or more homology to the germ-line sequence based on the observation that polymorphisms may lead to 2% difference in the DNA sequence of alleles within the immunoglobulin loci. 1

The degree of homology to the germ-line sequence that optimally delineates these 2 clinical subsets of CLL remains controversial. Both of the original studies2, 3 demonstrating the prognostic significance of IgVH gene mutational status found that a 98% cutoff provided the optimum discrimination, but recently a 97% or 95% cutoff was found to provide better discrimination. 4, 5 In addition, cases using the VH3-21 and possibly the VH3-23 gene segments are associated with a poor prognosis regardless of their mutational status. 6, 7 In this study we have sequenced the corresponding germ-line IgVH gene from the neutrophils of a number of patients with CLL whose rearranged IgVH gene showed between 96.6% and 99.6% homology to the germ-line database sequence, in order to determine the relative incidence of polymorphisms and point mutations in cases with a low mutational load. Germ-line IgVH sequences were obtained from all 13 cases analyzed. Clinical stage, IgVH gene usage, and percent homology to the germ-line sequence are shown in Table 1. Analysis of the granulocytes sequence showed that 70 of the 72 base changes observed in the lymphocytes were absent in the corresponding germ-line sequence. However, polymorphisms did account for the