Abstract:Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in western countries, but its incidence in China is relatively low. The discordance in the incidence has been attributed to different genetic background among ethics groups. Immunoglobulin heavy chain variable region gene (IGHV), as part of encoding genes for B cell receptor, represents one of the most important prognostic factors for CLL patients. In this study, we retrospectively analyzed the IGHV gene features of 291 newly diagnosed CLL patients from our institution, and found that the usage of IGHV gene fragments in Chinese CLL patients was significantly different from that of western CLL patients: Chinese CLL patients had higher frequency of IGHV3-7 and IGHV4-39 usage and lower frequency of IGHV1-69 usage. Among the two gene fragments with higher usage rate, IGHV4-39 was associated with a shorter time to first treatment, and was also associated with several unfavorable prognostic markers including advanced stage of disease, trisomy 12, NOTCH1 mutation and CD49d expression. These results highlight IGHV gene usage feature as an important prognostic marker for CLL, and suggest the over-usage of IGHV4-39 in Chinese CLL patients may related to poor prognosis, which warrant further investigation.