NUP98-DDX10融合基因阳性急性白血病2例并文献复习

Acute leukemia with NUP98-DDX10 fusion gene-positive:report of 2 cases and review of literature

目的探讨NUP98-DDX10融合基因阳性急性白血病(AL)患者的临床特点、诊断和治疗方法及预后。方法回顾性分析分别于2020年4月和2021年2月就诊于中国医学科学院血液病医院的2例NUP98-DDX10融合基因阳性AL患者的临床资料。采用转录组基因测序检测融合基因,并应用反转录-聚合酶链反应扩增融合基因片段行Sanger测序明确序列,分析患者临床及实验室指标的特征,并进行文献复习。结果经临床诊断,例1为急性髓系白血病M5型(AML-M5),例2为急性混合表型白血病无法分类型(ALAL-NOS);例1以严重出凝血异常起病,初诊时达到弥散性血管内凝血(DIC)临床诊断标准。2例患者转录组测序发现NUP98-DDX10融合基因阳性,并经反转录-聚合酶链反应证实。测序识别出两种不同剪接融合模式:一种是NUP98的第14号外显子与DDX10的第7号外显子融合,既往称为Ⅱ型;另一种是未见报道的剪接融合模式,NUP98的第14号外显子与DDX10的第13号外显子融合,将其命名为Ⅳ型。1997至2018年文献共报道16例NUP98-DDX10相关血液肿瘤,与本次报道的2例汇总分析,18例患者中男13例,女5例;中位年龄为31.5岁(0.08~61岁),中位生存期12个月(1~46个月)。结论在ALAL-NOS患者中识别一种NUP98-DDX10新的融合转录本。伴有NUP98-DDX10融合基因的血液肿瘤十分罕见,常规治疗反应差,需要通过异基因造血干细胞移植改善预后。

Objective To investigate the clinical characteristics,diagnosis,treatment and prognosis of acute leukemia(AL)with NUP98-DDX10 fusion gene-positive.Methods The clinical data of 2 AL patients with NUP98-DDX10 fusion gene-positive who admitted to Blood Diseases Hospital,Chinese Academy of Medical Sciences in April 2020 and February 2021,respectively were retrospectively analyzed.Transcriptome gene sequencing was used to detect fusion gene,and the fusion gene fragment was amplified by using reverse transcription polymerase chain reaction(RT-PCR),and Sanger sequencing was used to clarify sequences.The clinical and experimental indicators characteristics were analyzed and the relevant literatures were reviewed.Results According to the clinical diagnosis,1 patient was diagnosed as acute myeloid leukemia M5(AML-M5)and 1 patient was diagnosed as acute leukemia of ambiguous lineage,not otherwise specified(ALAL-NOS).The AML-M5 patient presented with severe coagulation abnormalities,and fulfilled the diagnostic criteria for diffuse intravascular coagulation(DIC)at the initial visit.Transcriptome sequencing of 2 patients showed NUP98-DDX10 fusion gene-positive.RT-PCR confirmed that sequencing results identified 2 different splice fusion modes:one was NUP98 exon 14 fused with DDX10 exon 7(usually called"typeⅡ"),the other was NUP98 exon 14 fused with DDX10 exon 13,which was never reported and named as"typeⅣ".From 1997 to 2018,a total of 16 cases with NUP98-DDX10 related hematologic neoplasms were reported in the literature.A summary analysis of 16 cases added with 2 patients in our center included 13 males and 5 females with median age 31.5 years(0.08-61 years).The median overall survival was 12 months(1-46 months).Conclusions A novel fusion gene NUP98-DDX10 transcriptome is identified in ALAL-NOS patient.Hematological malignancies with NUP98-DDX10 are very rare.They respond poorly to conventional treatment and require allogeneic hematopoietic stem cell transplantation(allo-HSCT)to improve the prognosis.