634 例中国骨髓增生异常综合征患者细胞遗传学和分子遗传学异常的临床意义。
Clinical significance of cytogenetic and molecular genetic abnormalities in 634 Chinese patients with myelodysplastic syndromes.
机构信息
Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Myelodysplastic Syndromes Diagnosis and Therapy Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
出版信息
Cancer Med. 2021 Mar;10(5):1759-1771. doi: 10.1002/cam4.3786. Epub 2021 Feb 20.
PURPOSE
To explore the relevance of cytogenetic or molecular genetic abnormalities to clinical variables, including clinical and laboratory characteristics and prognosis in Chinese patients with myelodysplastic syndromes (MDS).
METHODS
A total of 634 consecutive patients diagnosed with MDS at The First Affiliated Hospital, Zhejiang University School of Medicine from June 2008 to May 2018 were retrospectively included in this study. All patients had evaluable cytogenetic analysis, and 425 patients had MDS-related mutations sequencing.
RESULTS
38.6% of patients displayed abnormal karyotypes. The most common cytogenetic abnormality was +8 (31%). Sole +8 was related to female (p = 0.002), hemoglobin >10 g/dL (p = 0.03), and <60 years old (p = 0.046). TP53 mutations were associated with complex karyotype (CK) (p < 0.001). DNMT3A mutations correlated with -Y (p = 0.01) whereas NRAS mutations correlated with 20q- (p = 0.04). The overall survival (OS) was significantly inferior in patients with +8 compared with those with normal karyotype (NK) (p = 0.003). However, the OS of sole +8 and +8 with one additional karyotypic abnormality was not different from NK (p = 0.16), but +8 with two or more abnormalities had a significantly shorter OS than +8 and +8 with one additional karyotypic abnormality (p = 0.02). In multivariable analysis, ≥60 years old, marrow blasts ≥5% and TP53 mutations were independent predictors for poor OS (p < 0.05), whereas SF3B1 mutations indicated better prognosis. Male IDH1 and IDH2 mutations and marrow blasts ≥5% were independent risk factors for worse leukemia free survival (LFS) (p < 0.05).
CONCLUSION
In this population of Chinese patients, trisomy 8 is the most common karyotypic abnormality. Patients with +8 showed a poorer OS compared with patients with NK. Sole +8 and +8 with one additional karyotypic abnormality had similar OS with NK, whereas +8 with two or more abnormalities had a significantly shorter OS. DNMT3A mutations correlated with -Y and NRAS mutations correlated with 20q-. TP53 mutations were associated with CK and had a poor OS. SF3B1 mutations indicated a favorable OS. IDH1 and IDH2 mutations independently indicated inferior LFS.
目的
探讨细胞遗传学或分子遗传学异常与临床变量的相关性，包括临床和实验室特征及预后，在中国骨髓增生异常综合征（MDS）患者中。
方法
本研究回顾性纳入 2008 年 6 月至 2018 年 5 月期间在浙江大学医学院附属第一医院诊断为 MDS 的 634 例连续患者。所有患者均进行了可评估的细胞遗传学分析，425 例患者进行了 MDS 相关基因突变测序。
结果
38.6%的患者显示染色体核型异常。最常见的细胞遗传学异常为+8（31%）。单纯+8与女性（p=0.002）、血红蛋白＞10g/dL（p=0.03）和＜60 岁（p=0.046）相关。TP53 突变与复杂核型（CK）相关（p＜0.001）。DNMT3A 突变与-Y 相关（p=0.01），而 NRAS 突变与 20q-相关（p=0.04）。与正常核型（NK）相比，+8 患者的总体生存（OS）显著降低（p=0.003）。然而，单纯+8 和+8 加一种额外染色体异常的 OS 与 NK 无差异（p=0.16），但+8 加两种或更多异常的 OS 明显短于+8 和+8 加一种额外染色体异常（p=0.02）。多变量分析显示，年龄≥60 岁、骨髓原始细胞≥5%和 TP53 突变是 OS 不良的独立预测因素（p＜0.05），而 SF3B1 突变提示预后较好。男性 IDH1 和 IDH2 突变以及骨髓原始细胞≥5%是无白血病生存（LFS）较差的独立危险因素（p＜0.05）。
结论
在本研究的中国患者人群中，三体 8 是最常见的核型异常。与 NK 相比，+8 患者 OS 较差。单纯+8 和+8 加一种额外染色体异常的 OS 与 NK 相似，而+8 加两种或更多异常的 OS 明显短于+8 和+8 加一种额外染色体异常。DNMT3A 突变与-Y 相关，NRAS 突变与 20q-相关。TP53 突变与 CK 相关，OS 不良。SF3B1 突变提示 OS 良好。IDH1 和 IDH2 突变独立提示 LFS 较差。
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