The mutational status and configuration of immunoglobulin heavy variable (IGHV) 
gene rearrangements was analyzed in 85 Serbian patients with chronic lymphocytic 
leukemia (CLL). We found that 55.3% of cases belonged to mutated and 44.7% to 
unmutated CLL, progressive disease predominating in the unmutated subset. IGHV 
gene use resembled that obtained for Mediterranean countries, except for 
underrepresentation of the IGHV4 subgroup in our cohort.
BACKGROUND: Chronic lymphocytic leukemia (CLL) results from the clonal expansion 
of mature B lymphocytes and is characterized by extreme clinical heterogeneity. 
One of the most reliable prognostic markers in chronic lymphocytic leukemia 
(CLL) is the mutational status of immunoglobulin heavy variable (IGHV) genes, 
which defines 2 subsets, mutated CLL (M-CLL) and unmutated CLL (U-CLL), with 
different clinical courses. Biased IGHV gene use between M-CLL and U-CLL clones, 
as well as population differences in the IGHV gene repertoire have been 
reported.
PATIENTS AND METHODS: In this study, mutational status and configuration of 
IGHV-IGHD-IGHJ rearrangements in 85 Serbian patients were analyzed using reverse 
transcriptase-polymerase chain reaction (RT-PCR) and sequencing methodology.
RESULTS: We found that 55.3% of cases belonged to M-CLL and 44.7% belonged to 
U-CLL, with progressive disease predominating in the unmutated subset. Most 
frequently expressed was the IGHV3 subgroup (55.7%), followed by IGHV1 (27.3%), 
IGHV4 (12.5%), IGHV5 (2.3%), IGHV2 (1.1%), and IGHV6 (1.1%). The distribution of 
IGHD subgroups was as follows: IGHD3, 39.1%; IGHD2, 21.8%; IGHD6, 12.6%; IGHD1, 
10.3%; IGHD4, 8%; IGHD5, 6.9%; and IGHD7, 1.1%. The most frequent IGHJ gene was 
IGHJ4 (48.9%), followed by IGHJ6 (28.4%), IGHJ3 (11.4%), and IGHJ5 (11.4%). In 
15.3% of cases, heavy complementarity-determining region 3 (VH CDR3) amino acid 
sequences could be assigned to previously defined stereotyped clusters.
CONCLUSIONS: Our study showed a strong correlation between IGHV gene mutational 
status and clinical course of CLL. IGHV gene use was comparable to that obtained 
for Mediterranean countries, with the exception of the IGHV4 subgroup, which was 
underrepresented in our cohort.