Wang T, Ni J B, Wang X Y, Dai Y, Ma X L, Su Y C, Gao Y Y, Chen X, Yuan L L, Liu H X
Department of Pathology & Laboratory Medicine, Hebei Yanda Lu Daopei Hospital, Langfang 065201, China.
Beijing Lu Daopei Institute of Hematology, Beijing 100176, China.
Zhonghua Yi Xue Za Zhi. 2019 Sep 24;99(36):2820-2825. doi: 10.3760/cma.j.issn.0376-2491.2019.36.005.
To investigate the genetic characteristics and clinical outcomes of pediatric acute myeloid leukemia patients with NUP98-NSD1 fusion gene. 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. 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. 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.
探讨伴有NUP98-NSD1融合基因的儿童急性髓系白血病患者的遗传学特征及临床结局。本研究共纳入80例儿童急性髓系白血病患者，在初诊及复发时采集骨髓标本。采用荧光原位杂交（FISH）和聚合酶链反应（PCR）检测NUP98-NSD1。对NUP98-NSD1阳性病例进一步分析其他实验室检查结果及临床结局。共有8例患者（10.0%）NUP98-NSD1阳性，均为NUP98外显子12与NSD1外显子6的融合。根据法美英分类，有2例M2、3例M4和3例M5病例。7例患者初诊时有核型结果，均无复杂核型异常。其中，2例核型正常，3例8号染色体三体，1例6号染色体三体，2例涉及9q13或9q21异常。在疾病进展或复发过程中观察到额外的核型异常及克隆演变，5例有9q13或9q32异常。5例（62.5%）FLT3-ITD突变阳性。患者接受DAE/NAE/HAE/IA化疗。3例患者经过几个疗程化疗未达到缓解，5例达到缓解但在1至19个月后复发。5例患者接受挽救性异基因造血干细胞移植（allo-HSCT）。其中，4例在移植后40天至4个月死亡，1例存活至末次随访8.5个月。NUP98-NSD1是一种具有显著临床预后意义的复发性基因异常，该组疾病具有独特的临床和遗传学特征。对于新诊断、难治及复发的儿童急性髓系白血病患者，应采用FISH或PCR检测NUP98-NSD1，以识别高危基因标志物。
