Clinical implications of NUP98::NSD1 fusion at diagnosis in adult FLT3-ITD positive AML

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 mult...

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Published in:European journal of haematology 2023-10, Vol.111 (4), p.620-627
Main Authors: 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
Format: Article
Language:English
Subjects:
Acute myeloid leukemia
Anthracycline
Chemotherapy
Cytarabine
Diagnosis
Hematopoietic stem cells
Mutation
Patients
Pediatrics
Remission
Stem cell transplantation
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Summary: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.
ISSN:0902-4441
1600-0609
1600-0609
DOI:10.1111/ejh.14055