It is well known that the mutational status of IGHV carries a strong prognostic value in CLL, with patients carrying unmutated genes having a more aggressive course of the disease, as reflected in a shorter life expectancy.31,32 Despite the limited size of the prediagnostic clones and limited availability of specimens, we were able to define IGHV mutational status for 35 of 45 clones, demonstrating that the vast majority (approximately 80%) carried mutated IGHV genes. This finding notwithstanding, patients with unmutated genes were also observed, some with 100% identity with the closest germ-line genes. The distribution of mutated clones, as compared with unmutated clones, was very similar regardless of the time between the time at which the blood sample was obtained and the subsequent CLL diagnosis. In addition, among eight unmutated prediagnostic clones, three were present more than 3 years before the CLL diagnosis, with two being detectable 5 years before.
