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摘要: 目的 探讨SET-NUP214融合基因阳性急性白血病的临床特征及意义。方法 回顾性分析2016年1月—2020年12月我院收治的SET-NUP214融合基因阳性急性白血病患者的临床资料，结合患者白血病免疫分型、染色体核型分析、荧光原位杂交技术、微小残留病、T细胞受体基因重排、突变基因及融合基因进行分析。结果 本组SET-NUP214融合基因阳性急性白血病共13例，男11例，女2例; 中位年龄36(18~50)岁; 其中急性T淋巴细胞白血病/淋巴母细胞淋巴瘤10例，在同期成人急性T淋巴细胞白血病中发生率为12.20%(10/82)。免疫分型常伴有髓系标志表达。8例行染色体核型检测，其中4例为正常核型; 10例行突变基因检测，其中2例伴PHF6突变，2例伴NOTCH1突变，2例伴JAK3突变。11例接受化疗，其中7例在诱导化疗期间死亡或对化疗产生耐药性，3例达缓解后接受造血干细胞移植。结论 SET-NUP214融合基因阳性急性白血病多见于中青年男性急性T淋巴细胞白血病，常伴有PHF6及NOTCH1基因突变，可从异基因造血干细胞移植中获益，SET-NUP214表达水平可作为微小残留病随访及预后的监测指标，需进一步扩大样本量加以证实。
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关键词:
- 急性T淋巴细胞白血病 /
- 急性髓系白血病 /
- SET-NUP214融合基因 /
- 临床特征
Abstract: Objective To investigate the characteristics and prognostic significance of hematological malignancies in patients with theSET-NUP214fusion gene.Methods Clinical data of patients with acute leukemia harboring theSET-NUP214fusion gene in our hospital from January 2016 to December 2020 were retrospectively analyzed. The flow cytometry, karyotype, the minimal residual disease detection(MRD), fluorescence in situ hybridization(FISH), T cell receptor gene rearrangement(TCR), mutant gene and fusion gene were analyzed.Results A total of 13 acute leukemia patients with positiveSET-NUP214were enrolled, including 11 males and 2 females, with a median age of 36 years(18-50 years). There were 10 cases of T-cell acute lymphoblastic leukemia/lymphoma(T-ALL/T-LBL), accounting for 12.20%(10/82) of adult T-ALL in the same period. It was often associated with the expression of myeloid lineage markers. The chromosome karyotype was detected in 8 patients, of which 4 cases were normal karyotype. Ten patients underwent mutation gene detection, including 2 cases withPHF6mutation, 2 cases withNOTCH1mutation and 2 cases withJAK3mutation. Eleven patients received chemotherapy and 7 cases died or showed chemotherapy resistance during induction chemotherapy, of which 3 patients received hematopoietic stem cell transplantation after remission.Conclusion SET-NUP214fusion gene positive acute leukemia is more common in young and middle-aged men with T-ALL, often accompanied byPHF6andNOTCH1gene mutations, which can benefit from allogeneic hematopoietic stem cell transplantation. The expression level ofSET-NUP214can be used as a monitoring indicator for the follow-up and prognosis of MRD, which needs to be confirmed by further expanding the sample size. -
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表 1 13例SET-NUP214融合基因阳性急性白血病患者的临床特征
病例 性别 年龄/岁 症状 髓外浸润 发病时间/d 1 男 41 恶心、纳差、乏力 腋窝多发淋巴结 1 2 女 30 下肢瘀斑 脾脏 30 3 男 23 发热、胸闷 颈部淋巴结、脾脏 30 4 男 22 颈部肿块 全身多发淋巴结、脾脏 30 5 男 23 发热、头痛 无 6 6 男 18 恶心、呕吐、头痛 全身多发淋巴结、肝脏、脾脏 7 7 男 48 发热 脾脏 15 8 男 41 颈部肿块 颈部多发淋巴结 30 9 女 29 颈部肿块 全身多发淋巴结 60 10 男 42 发热、乏力、头晕 全身多发淋巴结、脾脏 30 11 男 44 皮疹、发热、水肿 无 30 12 男 50 发热、颈部肿块 不详 90 13 男 36 骨关节痛、颈部肿块 颈部淋巴结、脾脏 30 
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表 2 13例SET-NUP214融合基因阳性急性白血病患者的实验室特征
病例 白细胞计数/(×109·L-1) 骨髓原始细胞/% 免疫表型 染色体核型 基因突变 诊断 1 21.30 92.8 CD34，CD33，CD38，CD7，CD71，CD123 46，XY[5] 阴性 AML-M0 2 19.72 92.8 CD34，CD33str，CD7，CD38，CD123，CD71 46，XX，del(9)(q11)[5] PHF6 AML-M1 3 1.30 86.8 CD34，CD13，CD33，CD123，CD7，CD38，CD71 46，XY[15] 不详 AML-M2 4 6.90 89.2 CD5，CD7，CD38，CD71，TdT 46，XY，del(9)(q11q34) [2]/46，XY[5] NOTCH1，JAK3 T-ALL 5 0.10 73.0 CD7，CD45dim，CD38，CD117，CD99，CD5，CD71 TCRβ基因重排 阴性 T-ALL 6 93.80 86.4 CD7，CD5dim，CD3dim，CD38，CD71，cCD3 不详 PHF6，JAK3 T-ALL 7 232.90 94.4 CD7，CD71 不详 阴性 T-ALL 8 76.12 89.6 CD7，CD5，CD38，CD71，cCD3 46，XY[1] NOTCH1，JAK1 T-ALL 9 2.00 50.4 CD34，CD7，CD38，cCD3，TdT 46，XX[4] 阴性 T-LBL 10 3.41 91.6 CD34，CD7，CD5，CD38，CD71，cCD3 近三倍体和近四倍体 阴性 T-ALL 11 96.20 94.4 CD34，CD7，CD5，CD33，CD38，CD71，cCD3 不详 不详 T-ALL 12 24.00 94.4 CD3，cCD3，CD5，CD13，CD33 不详 不详 T-ALL 13 317.00 93.6 CD34，CD7，CD38，CD71，cCD3dim 不详 阴性 T-ALL
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表 3 13例SET-NUP214融合基因阳性急性白血病患者的治疗及疗效
病例 诱导方案 化疗反应 移植 结局 总生存期/月 1 DA 死亡 否 死亡 0.3 2 IA CR 否 CR，存活 12.0 3 DA 未缓解 否 放弃，死亡 1.0 4 VDCLP CR 亲缘不全相合 移植物抗宿主病，死亡 8.0 5 VDCLP CR 同胞全相合 CR，存活 16.0 6 VDLD 部分缓解 同胞全相合 CR，存活 27.0 7 CNOP 死亡 否 死亡 0.5 8 无 无化疗 否 放弃，死亡 1.0 9 Hyper-CAVD A 死亡 否 死亡 0.8 10 Hyper-CAVD B 未缓解 否 放弃，死亡 2.0 11 无 无化疗 否 放弃，死亡 1.0 12 VDCLP 死亡 否 意识丧失，死亡 0.7 13 Hyper-CAVD B 未缓解 否 CR，存活 3.0 DA：柔红霉素/阿糖胞苷; IA：伊达比星/阿糖胞苷; VDCLP：长春地辛/柔红霉素/环磷酰胺/门冬酰胺酶/地塞米松; VDLD：长春地辛/多柔比星/门冬酰胺酶/地塞米松; CNOP：环磷酰胺、米托蒽醌/长春地辛/地塞米松; Hyper-CAVD A：环磷酰胺/多柔比星/长春地辛/地塞米松; Hyper-CAVD B：甲氨蝶呤/阿糖胞苷。
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