Miyajima Toru, Onozawa Masahiro, Yoshida Shota, Miyashita Naoki, Kimura Hiroyuki, Takahashi Shogo, Yokoyama Shota, Matsukawa Toshihiro, Goto Hideki, Sugita Junichi, Fujisawa Shinichi, Hidaka Daisuke, Ogasawara Reiki, Mori Akio, Matsuoka Satomi, Shigematsu Akio, Wakasa Kentaro, Kasahara Ikumi, Saga Tomoyuki, Hashiguchi Junichi, Takeda Yukari, Ibata Makoto, Yutaka Tsutsumi, Fujimoto Katsuya, Kondo Takeshi, Teshima Takanori
Department of Hematology, Graduate School of Medicine, Hokkaido University Faculty of Medicine, Sapporo, Japan.
Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, Japan.
Eur J Haematol. 2023 Oct;111(4):620-627. doi: 10.1111/ejh.14055. Epub 2023 Jul 19.
The cryptic fusion oncogene NUP98::NSD1 is known to be associated with FLT3-ITD mutation in acute myeloid leukemia (AML), and an independent poor prognostic factor in pediatric AML. However, there are little data regarding the clinical significance of NUP98::NSD1 in adult cohort.
We conducted a multicenter retrospective study to investigate the prevalence, clinical characteristics, and prognostic impact of NUP98::NSD1 in adult FLT3-ITD-positive AML patients.
In a total of 97 FLT3-ITD-positive AML patients, six cases (6.2%) were found to harbor the NUP98::NSD1 fusion transcript. NUP98::NSD1 positive cases had significantly higher platelet counts and a higher frequency of FAB-M4 morphology than NUP98::NSD1 negative cases. NUP98::NSD1 was found to be mutually exclusive with NPM1 mutation, and was accompanied by the WT1 mutation in three of the six cases. The presence of NUP98::NSD1 fusion at the time of diagnosis predicted poor response to cytarabine-anthracycline-based intensive induction chemotherapy (induction failure rate: 83% vs. 36%, p = .038). Five of the six cases with NUP98::NSD1 underwent allogeneic hematopoietic stem cell transplantation (HSCT). Two of the five cases have successfully maintained remission, with one of them being rescued through a second HSCT.
Detecting NUP98::NSD1 in adult FLT3-ITD-positive AML is crucial to recognizing chemotherapy-resistant group.
隐匿性融合癌基因NUP98::NSD1已知与急性髓系白血病（AML）中的FLT3-ITD突变相关，并且是儿童AML中一个独立的不良预后因素。然而，关于NUP98::NSD1在成人队列中的临床意义的数据很少。
我们进行了一项多中心回顾性研究，以调查NUP98::NSD1在成人FLT3-ITD阳性AML患者中的发生率、临床特征和预后影响。
在总共97例FLT3-ITD阳性AML患者中，发现6例（6.2%）携带NUP98::NSD1融合转录本。与NUP98::NSD1阴性病例相比，NUP98::NSD1阳性病例的血小板计数显著更高，且FAB-M4形态的频率更高。发现NUP98::NSD1与NPM1突变相互排斥，6例中有3例伴有WT1突变。诊断时NUP98::NSD1融合的存在预示着对基于阿糖胞苷-蒽环类药物的强化诱导化疗反应不佳（诱导失败率：83%对36%，p = 0.038）。6例NUP98::NSD1患者中有5例接受了异基因造血干细胞移植（HSCT）。5例中有2例成功维持缓解，其中1例通过第二次HSCT获救。
在成人FLT3-ITD阳性AML中检测NUP98::NSD1对于识别化疗耐药组至关重要。
