Objective: To investigate the genetic characteristics and clinical outcomes of pediatric acute myeloid leukemia patients with NUP98-NSD1 fusion gene. Methods: A total of 80 pediatric AML patients were enrolled in this study, and bone marrow specimens were collected at initial diagnosis and relapse. NUP98-NSD1 was screened by fluorescence in situ hybridization (FISH) and PCR. Other laboratory test results and clinical outcomes were further analyzed for the NUP98-NSD1 positive cases. Results: A total of eight patients (10.0%) were positive for NUP98-NSD1, which were all fusions of NUP98 exon12 and NSD1 exon 6. There were two M2, three M4, and three M5 cases according to the French-American-British classification. Seven patients had karyotype results at the time of initial diagnosis, and none of them had complicated karyotype abnormalities. Among these patients, two cases had normal karyotype, three cases had trisomy 8, one case had trisomy 6, and two cases had anomalies involving 9q13 or 9q21. Additional karyotypic abnormalities and clonal evolutions were observed during disease progression or relapse, five cases had 9q13 or 9q32 abnormalities. Five cases (62.5%) were positive with FLT3-ITD mutation. Patients were treated with DAE/NAE/HAE/IA chemotherapy. Three cases did not achieve remission after several courses of chemotherapy, and five cases achieved remission but relapsed in 1 to 19 months. Five cases underwent salvage allogeneic hematopoietic stem cell transplantation (allo-HSCT). Among whom, four died in 40 days to 4 months after transplantation, and one survived 8.5 months till the last follow-up. Conclusions: NUP98-NSD1 is a recurrent genetic abnormality with significant clinical prognostic significance, and this group of disease has unique clinical and genetic characteristics. NUP98-NSD1 should be screened by FISH or PCR for children with AML who are newly diagnosed or refractory and relapsed to identify the high-risk genetic marker.
目的： 探讨NUP98-NSD1融合基因阳性儿童急性髓性白血病（AML）的遗传学特征和临床疗效。 方法： 采集在河北燕达陆道培医院就诊的80例儿童AML患者初诊和复发时骨髓标本，用荧光原位杂交（FISH）和PCR法检测NUP98-NSD1，对阳性患者进一步分析其他实验室检查结果和临床治疗转归。 结果： 共8例（10.0%）患者NUP98-NSD1阳性，均为NUP98外显子12与NSD1外显子6的融合，按血细胞形态学的法美英分型标准2例为M2、3例为M4、3例为M5。7例患者有初诊时染色体核型结果，均不伴复杂核型异常，其中2例为正常核型、3例伴8号染色体三体（+8）、1例伴6号染色体三体（+6）、2例分别伴涉及9q13和9q21的异常。患者在疾病进展或复发时均检测到新的核型异常和克隆演变，5例伴9q13或9q32异常。伴FLT3-ITD突变阳性患者5例（62.5%）。分别给予DAE/NAE/HAE/IA方案化疗，3例患者经多个疗程化疗始终不缓解，5例患者获得血液学缓解但于1~19个月复发。5例患者进行了挽救性异基因造血干细胞移植，4例于移植后40 d~4个月死亡，1例截至随访日存活8.5个月。 结论： NUP98-NSD1为具有显著临床预后意义的重现性遗传学异常，这组疾病具有独特的临床和遗传学特征。对于初诊和难治复发的儿童AML患者，应采用FISH或PCR方法筛查NUP98-NSD1融合基因，鉴定该高危异常。.
Keywords: Child; Gene fusion; Hematopoietic stem cell transplantation; Leukemia, myeloid, acute.