The specific distribution pattern of IKZF1 mutation in acute myeloid leukemia
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The specific distribution pattern of IKZF1 mutation in acute myeloid leukemia Xiang Zhang1,2 , Xuewu Zhang1,2, Xia Li1,2, Yunfei Lv1,2, Yanan Zhu1,2, Jinghan Wang1,2, Jie Jin1,2* and Wenjuan Yu1,2*
Abstract IKZF1 belongs to the IKAROS family of transcription factors, and its deletion/mutation frequently affects acute lymphoblastic leukemia. In acute myeloid leukemia, IKZF1 deletion has been demonstrated recurrent, but whether IKZF1 mutation also exists in AML remained largely unknown. Herein, we analyzed the IKZF1 mutation in AML. In our cohort, the frequency of IKZF1 mutation was 2.6% (5/193), and 5 frameshift/nonsense mutations as well as 2 missense mutations were identified in total. Molecularly, IKZF1 mutation was absent in fusion gene-positive AML, but it was demonstrated as the significant concomitant genetic alteration with SF3B1 or bi-allele CEBPA mutation in AML. Clinically, two IKZF1, PTPN11 and SF3B1-mutated AML patients exhibited one aggressive clinical course and showed primary resistant to chemotherapy. Furthermore, we confirmed the recurrent IKZF1 mutation in AML with cBioPortal tool from OHSU, TCGA and TARGET studies. Interestingly, OHSU study also showed that SF3B1 mutation was the significant concomitant genetic alteration with IKZF1 mutation, indicating their strong synergy in leukemogenesis. In conclusion, IKZF1 mutation recurrently affected AML. Keywords: IKZF1 mutation, Acute myeloid leukemia, Recurrence IKZF1 belongs to the IKAROS family of transcription factors. It contains four zinc fingers at the N-terminal that directly bind to DNA at the core motif A/GGAAA and additional two zinc fingers at the C-terminal required for forming homo- and hetero-dimerization between different IKZF proteins [1]. DNA binding activity of IKZF1 can be enhanced by its dimerization, so both DNA-binding and dimer-forming defects alter IKZF1 function. IKZF1 deletions and mutations have been reported to affect B-cell precursor ALL and contribute to its poor prognosis [2]. IKZF1 alterations are less studied in AML. Recurrent IKZF1 deletions have been identified in AML [3, 4], but whether IKZF1 mutations affect AML
*Correspondence: [email protected]; [email protected] 1 Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Rd Zhejiang Province, Hangzhou 310003, China Full list of author information is available at the end of the article
in general remains unknown. Herein, we analyzed IKZF1 mutation in AML. A total of 193 adult AML patients, who subjected to TES, were retrospectively analyzed in our center (01/05/2018–29/02/2020), while APL was excluded. Among these patients, 100 were male and 93 were female, and the median age was 56 (range 18–82). A total of 169 patients were diagnosed with de novo AML, 10 with refractory/relapsed AML, 6 with MDS/AML, 5 with MLL (5 de novo cases), and 3 with MS/AML (1 de novo case, 2 refractory/relapsed cases). The panel of TES included 236 genes recurrently mutated in hematological m
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