Immunoglobulin heavy chain variable region gene usage and mutational status of the leukemic B cells in Iranian patients with chronic lymphocytic leukemia

The mutational status of the immunoglobulin variable region heavy chain genes (IGHV) is an important prognostic marker in chronic lymphocytic leukemia (CLL). The data accumulated in the literature has largely been derived from studies conducted on Caucasian Western populations. Little is known about Asian CLL patients. In this study the IGHV genes usage and somatic hypermutation status have been investigated in 87 Iranian CLL patients. Based on a cut‐off of 98% nucleotide sequence homology, 64.4% and 35.6% of the patients expressed mutated and unmutated IGHV genes, respectively, with most non‐progressive patients being in the mutated group (35/44 vs 19/40; P = 0.009). Progression‐free survival (PFS) and time to first treatment (TTFT) were significantly higher in our mutated and non‐progressive patients compared to unmutated and progressive subtypes, respectively. The most frequently used IGHV gene was IGHV3‐7 (12.6%) followed by IGHV3‐30 (11.4%), IGHV3‐48 (9.2%), IGHV4‐39 (6.9%), and IGHV1‐8 (6.9%) genes, which taken together comprised nearly half of the IGHV genes expressed in the Iranian CLL patients. Of the IGHV genes, IGHV3‐7 was significantly over‐represented in non‐progressive compared to progressive CLL patients (P = 0.036), whereas IGHV1‐69 and IGHV1‐2 were expressed at a higher frequency in unmutated compared to mutated CLL patients (P