临床肿瘤学杂志

目的 探讨人白细胞抗原(HLA)Ⅰ类分子与急性髓细胞白血病(AML)伴核磷素(NPM1)突变和预后的关系。方法 收集2018年1月至2021年12月间在解放军联勤保障部队第九六O医院诊治的106例NPM1突变AML患者以及90例NPM1突变阴性AML患者。另外，选取同时期60例与AML患者没有血缘关系且无血液病的健康志愿者作为健康对照组。通过聚合酶链反应-序列特异性引物法检测所有受试者的HLAⅠ类基因分型。随访记录患者总生存期(OS)。使用预测软件工具寻找NPM1衍生免疫肽。采用Kaplan-Meier法绘制生存曲线，生存差异进行Log-rank检验。结果 NPM1突变AML组患者HLAⅠ类等位基因A02、B07、B40和C07的频率显著低于健康对照组，且B07和C07频率显著低于NPM1突变阴性组(P<0.05)。与不表达HLAⅠ类特定等位基因(A02、B07、B40、C07)的AML患者比较，表达至少1种HLAⅠ类特定等位基因的患者死亡率更低(43.28%vs. 79.49%,P<0.05)。Kaplan-Meier分析显示NPM1突变AML中HLAⅠ类分子阳性患者的中位OS更长(P<0.001)。Cox风险比例回归模型分析显示FMS样酪氨酸激酶3基因内部串联重复(FLT3-ITD)阴性、HLA-B07表达是影响NPM1突变AML患者OS的独立因素(P<0.05)。仅在FLT3-ITD突变阴性患者中，HLA-B7和HLA-C7阳性组患者的生存预后明显优于阴性组(P<0.05)。预测软件工具发现B40和B07的候选NPM1衍生免疫肽。结论 NPM1突变AML患者特定HLAⅠ类等位基因明显降低，且HLA-B07或C07抗原的存在与FLT3-ITD阴性的NPM1突变AML患者的更好生存相关。

Objective To investigate the relationship between human leukocyte antigen(HLA) class I molecules and acute myeloid leukemia(AML) with nucleophosmin(NPM1) mutation and prognosis. Methods A total of 106 patients with NPM1-mutated AML and 90 patients with NPM1-negative AML treated in the 960th Hospital of the Joint Logistics Support Force of the People's Liberation Army from January 2018 to December 2021 were collected. Additionally, 60 healthy volunteers without a blood relationship to AML patients and without hematological diseases during the same period were selected as a healthy control group. HLA class I genotyping was performed for all subjects using polymerase chain reaction-sequence specific primer method. The overall survival(OS) of the patients was recorded through follow-up. Predictive software tools were used to search for NPM1-derived immunopeptides. Results The frequencies of HLA class I alleles A02, B07, B40, and C07 in the NPM1-mutated AML group were significantly lower than those in the healthy control group, and the frequencies of B07 and C07 were significantly lower than those in the NPM1-negative group(P<0.05). Compared with AML patients who did not express specific HLA class I alleles(A02, B07, B40, C07), patients expressing at least one specific HLA class I allele had a lower mortality rate(P<0.05). Kaplan-Meier analysis showed that the median OS of HLA class I molecule-positive patients in NPM1-mutated AML was longer(P<0.001). Cox proportional hazards regression model analysis showed that FLT3-ITD negativity and HLA-B07 expression were independent factors affecting the OS of patients with NPM1-mutated AML(P<0.05). Only in patients negative for FLT3-ITD mutation, the survival prognosis of patients positive for HLA-B7 and HLA-C7 was significantly better than that of the negative group(P<0.05). Predictive software tools identified candidate NPM1-derived immunopeptides for B40 and B07.Conclusion The specific HLA class I alleles in NPM1-mutated AML patients are significantly reduced, and the presence of HLA-B07 or C07 antigens is associated with better survival in FLT3-ITD negative NPM1-mutated AML patients.