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Introduction: Although the prevalence of Asian chronic lymphocytic leukemia (CLL) patients is not as high as that of Caucasians, there are more atypical CLLs in Asia whose genetic characteristics and their clinical significance are distinct and remain unclear. Methods: A retrospective analysis of 85 CLL samples in our center was conducted from 2019 to 2022. We used next‐generation sequencing with a 172 gene panel to explore the multi‐gene mutational data and the mutational status of immunoglobulin heavy variable (IGHV) gene. Results: MYD88 (20.0%) was the most frequently mutated gene, much higher than in Europe, followed in order by TP53 (18.8%), NOTCH1 (14.1%), IGLL5 (11.8%), and DNMT3A (8.2%). In addition, the incidence of ATM and SF3B1 mutations was relatively lower in our centre compared to Europe. Mutated (M)‐IGHV patients were more likely to have a cooccurrence of MYD88 mutation, while complex karyotype and DNMT3A mutation were more common in the unmutated (U)‐IGHV group. MYD88 mutated CLL was characterized by prevalence in young males in high‐risk staging, with isolated 13q deletion and concomitant mutation of IGLL5. CLL patients with MYD88 and TP53 mutation showed an unfavorable prognosis. Conclusion: These results would be valuable in helping to understand the characteristics and significance of cytogenetic genetics in Chinese patients with CLL. [ABSTRACT FROM AUTHOR]