典型和不典型免疫表型慢性淋巴细胞白血病遗传学和分子生物学特征研究

OBJECTIVE: To analyze the differences in immunophenotype, cytogenetics, and molecular biology between typical and atypical immunophenotype chronic lymphocytic leukemia (CLL), and explore the correlation of cytogenetic anomalies with gene mutations. METHODS: This study included 488 patients diagnosed in the First Affiliated Hospital of Nanjing Medical University between November 2014 and May 2021. Of these, 382 patients scored 4–5 points, which was typical CLL (tCLL), and 106 scored 3 points, which was atypical CLL (aCLL) as per the Royal Marsden Hospital Immunomarker Integral System. Peripheral blood cells were collected for immunophenotype by multiparameter flow cytometry in 488 patients, fluorescence in situ hybridization (FISH) was employed to detect cytogenetic anomalies in 359 patients, and gene mutations were detected by next-generation sequencing (NGS) in 330 patients. RESULTS: The positive rates of CD10, CD22, CD49d, CD81, and FMC7 were significantly higher in the aCLL compared with the tCLL group (P＝0.020, P<0.001, P<0.001, P＝0.027, and P<0.001, respectively), while the positive rates of CD5, CD23, CD148, and CD200 were lower in the former compared to the latter (P<0.001, P＝0.017, P＝0.041, and P<0.001, respectively). aCLL exhibited a higher frequency of trisomy 12 and lower frequency of del (13q14) compared to the tCLL group (P<0.001 and P<0.001, respectively). Moreover, aCLL patients also showed a higher incidence of NOTCH1 mutations than the tCLL patients (P＝0.038), while no statistically significant differences in other gene mutations occurred between the two groups. No significant differences in overall survival (OS) and treatment-free survival (TFS) occurred between aCLL and tCLL using Kaplan-Meier analysis (P>0.05). CONCLUSION: aCLL has characteristic immunophenotype, cytogenetic, and somatic mutation that differ from tCLL, and this can provide reliable information for the diagnosis and differential diagnosis between the two groups.