Recurrent SETD2 mutation in NPM1 -mutated acute myeloid leukemia
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LETTER TO THE EDITOR
Open Access
Recurrent SETD2 mutation in NPM1mutated acute myeloid leukemia Jiewen Sun1, Wenjuan Yu2,3* and Xiang Zhang2,3*
Abstract SETD2 is the only methyltransferase for H3K36me3, and our previous study has firstly demonstrated that it functioned as one tumor suppressor in hematopoiesis. Consistent with it, SETD2 mutation, which led to its loss of function, was identified in AML. However, the distribution and function of SETD2 mutation in AML remained largely unknown. Herein, we integrated SETD2-mutated AML cases from our center and literature reports, and found that NPM1 mutation was the most common concomitant genetic alteration with SETD2 mutation in AML, with its frequency even higher than MLL rearrangement and AML1-ETO. Though this result indicated the cooperation of SETD2 and NPM1 mutations in leukemogenesis, our functional study showed that SETD2 was required for the proliferation of NPM1-mutated AML cell line OCI-AML3, but not MLL-rearranged AML cell line THP-1, via maintaining its direct target NPM1 expression, which was just opposite to its role of tumor suppressor. Therefore, we speculated that SETD2 possibly had two different faces in distinct subtypes and stages of AML. Keywords: SETD2 mutation, NPM1 mutation, Acute myeloid leukemia To the editor SETD2 has been demonstrated as one tumor suppresser in hematopoiesis [1], and SETD2 mutation affected AML, in which its distribution remained not fully understood [2]. Herein, we analyzed the SETD2 mutation in NPM1-mutated AML. One 36-year-old woman was committed due to abdominal pain and fever for 7 and 3 days, respectively. PB test showed WBC: 52.4 × 109/L, Hb: 98 g/L, PLT: 48 × 109/L, circulated blast: 80%. BM examination exhibited 67.5% myeblasts with the immunophenotype of CD11bCD13dim + CD14-CD15dim + CD33 + CD34partial + CD35CD38dim + CD45 + CD64-CD65dim + CD71 + CD117 + CD123dim + HLA-DR-. Though karyotype was normal and CBF or MLL rearrangements were negative, NPM1, SETD2, NRAS and ETV6 mutations were identified. * Correspondence: [email protected]; [email protected] 2 Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Rd, Zhejiang 310003, Hangzhou, China Full list of author information is available at the end of the article
Therefore, AML with mutated NPM1 was diagnosed. After receiving the operation for co-existed acute appendicitis, she accepted IA regimen as induction therapy, and CR1 was achieved. Subsequently, she received three cycle of medium-dose cytarabine regimen. However, AML relapsed at the 3 months after cessation of chemotherapy, and 72% myeloblasts re-emerged in BM. Due to the early recurrence, she accepted HAA and CLAG regimen successively, and achieved CR2. However, the leukemic clones were not eradicated reflected by persistent above mutations. Therefore, allogeneic semicompatible HSCT was immediately conducted. As follow-up, CR was still maintained at the 15 months after HSCT (Fig. 1a). In this patient, SETD2R2109X was identified, and it
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