ObjectiveTo explore the clinical characteristics of patients with diffuse large B-cell lymphoma (DLBCL) accompanied with KMT2D gene mutation and the impact of its co-mutated genes on prognosis. MethodsClinical data of 155 newly diagnosed DLBCL patients were obtained. The second-generation sequencing method was used to detect 475 hotspot genes, including KMT2D mutation. Patients were divided into the KMT2D mutation group and KMT2D wild-type group based on the presence or absence of KMT2D gene mutation. Clinical characteristics, differences in co-mutated genes, and survival differences between the two groups were compared. ResultsThe frequency of KMT2D mutation was 31%, which is predominantly observed in elderly patients (P=0.07) and less in the double-expressor phenotype (P=0.07). Compared with the KMT2D wild-type group, KMT2D gene mutation was associated with higher co-mutation rates of CDKN2A (OR=2.82, P=0.01) and BCL2 (OR=3.84, P=0.016), while being mutually exclusive with MYC gene mutation (OR=0.11, P=0.013). In univariate survival analysis, no statistically significant difference in overall survival (OS) was found between the KMT2D mutation group and the wild-type group (P=0.54). Further analysis of the prognostic significance of KMT2D with other gene mutations indicated that patients with KMT2DmutBTG2mut had poorer OS than those with KMT2Dwt BTG2mut (P=0.07) and KMT2Dwt BTG2wt (P=0.05). On the contrary, patients with KMT2Dmut CD79Bmut had better OS than those with KMT2Dmut CD79Bwt (P=0.09), with no prognostic impact observed for other co-mutated genes. Multivariate Cox regression analysis revealed that Ann Arbor stages Ⅲ and Ⅳ (HR=2.751, 95%CI: 1.169-6.472, P=0.02), elevated LDH levels (HR=2.461, 95%CI: 1.396-4.337, P=0.002), Ki-67 index>80% (HR=1.875, 95%CI: 1.066-3.299, P=0.029), and KMT2DmutBTG2mut(HR=4.566, 95%CI: 1.348-15.471, P=0.015) were independent risk factors for OS in patients with DLBCL (P<0.05). ConclusionDLBCL patients with KMT2D mutation often have multiple gene mutations, among which patients with a co-mutated BTG2 gene have poor prognosis.

Diffuse large B-cell lymphoma (DLBCL) demonstrates significant heterogeneity, investigations into the distinctions in clinical and molecular characteristics between Chinese Uygur and Han DLBCL patients remain unexplored. We retrospectively reviewed 279 DLBCL patients (105 Uygur and 174 Han patients), of which 155 patients underwent genetic profiling by NGS. Compared with Han patient, Uygur patients have better clinical prognostic indicators, including a higher proportion of patients with 0–1 extranodal involvement and I/II Ann Arbor staging. Consistently, Uygur patients were significantly associated with lower risk of relapse (P = 0.06), with a one-year relapse rate of 5

The aaIPI staging combination with molecular biology markers is more conducive to accurately judging the prognosis of young DLBCL patients. , and mutations predict worse survival in the patients with the aaIPI high-risk group.

The molecular landscapes of diffuse large B-cell lymphoma (DLBCL) remained to be comprehensively investigated with an urgent need to identify novel prognostic biomarkers guiding prognostic stratification and disease monitoring. Baseline tumor samples of 148 DLBCL patients were analyzed using targeted next-generation sequencing (NGS) for mutational profiling, whose clinical reports were retrospectively reviewed. In this cohort, the subgroup of old DLBCL patients (age at diagnosis > 60, N = 80) exhibited significantly higher Eastern Cooperative Oncology Group scores and International Prognostic Index than their young counterparts (age at diagnosis ≤ 60, N = 68). As revealed by the NGS results, PIM1 (43.9%), KMT2D (31.8%), MYD88 (29.7%), and CD79B (27.0%) were identified as the most frequently mutated genes. Aberrations of genes of the immune escape pathway were significantly enriched in the young subgroup, while the altered epigenetic regulators were more abundant in the old patients. FAT4 mutation was identified as a positive prognostic biomarker, associated with longer progression-free survival and overall survival in the entire cohort and the old subgroup, using the Cox regression analyses. However, the prognostic function of FAT4 was not reproduced in the young subgroup. We comprehensively analyzed the pathological and molecular characteristics of old and young DLBCL patients and demonstrated the prognostic value of FAT4 mutation, which requires further validation with sizable cohorts in future research.

目的 探讨弥漫性大B细胞淋巴瘤(DLBCL)ITPKB突变变异等位基因频率(VAF)与预后的相关性.方法 纳入2014年6月—2020年12月在新疆维吾尔自治区人民医院初次诊断的155例DLBCL患者,获取石蜡包埋的肿瘤组织标本.提取肿瘤组织DNA,应用二代测序技术检测包括ITPKB在内的475种热点基因,分析高频突变基因VAF与无进展生存(PFS)和总生存(OS)的关系.结果 ITPKB的突变频率为18.71％,ITPKB突变患者的PFS较未突变患者的PFS明显缩短,但差异无统计学意义(37.00 vs.108.00个月;HR=1.643,95％CI:0.920～2.934,P=0.093).通过基于R语言的网页工具探寻可区分患者预后的最佳VAF截断值,将患者依据VAF值分成对应的两组(高VAF组 vs.低VAF+野生型组),ITPKB最佳VAF的截断值为27.48％(HR=3.48,95％CI:1.70～7.13,P=0.00027),纳入年龄、性别、COO分型、IPI、LDH等临床指标行多因素Cox分析,结果显示PFS与高ITPKB VAF(≥28％)相关(HR=3.592,95％CI:1.738～7.425,P<0.001),是PFS独立的不良预测因素.结论 ITPKB突变高负荷为DLBCL患者PFS的独立危险因素,ITPKB突变的VAF在DLBCL患者中具有预后预测价值.

目的 探讨血清缺氧诱导因子1α(HIF-1α)、乳酸脱氢酶(LDH)、唾液酸(SA)水平对初诊骨髓增生异常综合征(MDS)疗效的预测价值.方法 选择初诊MDS患者86例(观察组),另选同期体检健康的志愿者33例(对照组),采集所有研究对象外周静脉血,离心留取血清,采用酶联免疫吸附试验检测血清HIF-1α、LDH、SA.以血清HIF-1α、LDH、SA水平的中位数为临界值,将初诊MDS患者分为血清HIF-1α、LDH、SA高水平者与低水平者.规范治疗4个疗程后,评价不同血清HIF-1α、LDH、SA水平初诊MDS患者疗效.采用受试者工作特征(ROC)曲线分析血清HIF-1α、LDH、SA水平对初诊MDS患者治疗未缓解的预测价值.结果 观察组血清HIF-1α、LDH、SA水平均高于对照组(P均<0.01).血清HIF-1α、LDH、SA高水平者分别为43、45、42例,其低水平者分别为43、41、44例,血清HIF-1α、LDH、SA低水平者疗效均优于其高水平者(P均<0.05).ROC曲线分析显示,血清HIF-1α、LDH、SA水平单独与三者联合预测初诊MDS患者治疗未缓解的曲线下面积分别为0.759、0.758、0.769、0.904,血清HIF-1α、LDH、SA水平联合预测初诊MDS患者治疗未缓解的曲线下面积高于三者单独(P均<0.05).结论 初诊MDS患者血清HIF-1α、LDH、SA水平显著升高,并且其水平与疗效有关;血清HIF-1α、LDH、SA水平对初诊MDS患者疗效均有一定预测价值,三者联合时预测价值更高.