Objective: To examine the survival rates and clinical characteristics of people with newly discovered non-M(3) acute myeloid leukemia (AML) who carry the ASXL1 gene mutation. Methods: From January 2016 to April 2021, the clinical information of patients with newly diagnosed non-M(3) AML at Shandong University's Qilu Hospital was retrospectively examined, and their clinical characteristics and survival were compared and analyzed. Gene mutation was detected by next-generation sequencing. Results: ① The study included 256 AML patients who were initially diagnosed and had complete data, including 47 cases of ASXL1 gene mutation-positive (ASXL1(+)) patients and 209 cases of ASXL1 gene mutation-negative (ASXL1(-)) patients. All patients were divided into three groups: elderly (≥60 years old, n=92) , middle-aged (45-59 years old, n=92) , and young (≤44 years old, n=72) . ②WBC, and age were higher in patients with ASXL1 mutations compared to ASXL1(-) patients, while complete response after the first round of treatment (CR(1)) was lower (P<0.05) . In the elderly group, WBC and the proportion of aberrant cells in nuclear cells in ASXL1(+) patients were higher than those in ASXL1(-) patients (P<0.05) . In the young group, the WBC of ASXL1(+) patients was higher than that of ASXL1(-) patients (z=-2.314, P=0.021) . ③IDH2 mutation and ASXL1 mutation was related (P=0.018, r=0.34) . In ASXL1(+) patients, the proportion of peripheral blasts in the high VAF group (VAF>40% ) was higher than that in the low VAF group (VAF<20% ) , and the proportion of aberrant nuclear cells was higher in the duplication and replacement mutation patients than in the deletion mutation patients (P<0.05) . ④The overall survival (OS) and progression-free survival (PFS) of ASXL1(+) patients were shorter than those of ASXL1(-) patients (median, 10 months vs 20 months, 10 months vs 17 months; P<0.05) . The proportion number of aberrant cells in nuclear cells (≥20% ) , complex karyotypes, and TET2 mutation were all independent risk variables that had an impact on the prognosis of ASXL1(+) patients, according to multivariate analysis (P<0.05) . Conclusion: ASXL1-mutated non-M(3) AML patients have higher WBC in peripheral blood, a higher proportion of aberrant cells in nuclear cells, lower CR(1) rate, and shorter OS and PFS. Additionally, a poor prognosis is linked to higher VAF, duplication, and substitution mutations in the ASXL1 gene, as well as the high proportion of aberrant cells in nuclear cells, complex karyotype, and TET2 mutation.
目的： 研究伴ASXL1基因突变初诊急性髓系白血病（AML）患者的临床特征及生存。 方法： 对2016年1月至2021年4月就诊于山东大学齐鲁医院的初诊非M(3)型AML患者的临床资料进行回顾性研究，分析ASXL1突变阳性患者的临床特征及生存。基因突变检测采用二代测序法。 结果： ①初诊且资料完整的256例AML患者纳入研究，其中ASXL1突变阳性（ASXL1(+)）47例，阴性（ASXL1(-)）209例。将所有患者分为老年组（≥60岁）92例、中年组（45~59岁）92例和青年组（≤44岁）72例。②与ASXL1(-)患者相比，ASXL1(+)患者年龄大、WBC高、首疗程完全缓解（CR(1)）率低（P值均<0.05）。老年组ASXL1(+)患者WBC、异常细胞占有核细胞比例高于ASXL1(-)患者（P值均<0.05）；青年组ASXL1(+)患者WBC高于ASXL1(-)患者（z＝-2.314，P＝0.021）。③ASXL1突变与IDH2突变相关（P＝0.018，r＝0.34）。在ASXL1(+)患者中，高变异等位基因频率（VAF）组（VAF>40%）外周血原始幼稚细胞比例高于低VAF组（VAF<20%），且碱基重复和替换突变患者的异常细胞占有核细胞比例高于缺失突变患者（P值均<0.05）。④ASXL1(+)患者中位总生存（OS）时间和无进展生存（PFS）时间均短于ASXL1(-)患者（10个月对20个月，10个月对17个月；P值均<0.05）。多因素分析示异常细胞占有核细胞比例≥20%、复杂核型、TET2突变均为影响ASXL1(+)患者预后的独立危险因素（P值均<0.05）。 结论： 伴ASXL1突变非M(3)型AML患者初诊时WBC、异常细胞占有核细胞比例均高，CR(1)率低，OS及PFS时间短。ASXL1突变患者中高VAF、碱基重复和替换突变与预后不良有关，异常细胞占有核细胞比例高、复杂核型和TET2突变均为影响预后的独立危险因素。.
Keywords: DNA mutational analysis; Gene, ASXL1; Leukemia, myeloid, acute; Survival analysis.