Letter to the Editor
Ann Lab Med 2021; 41(4): 443-446
Published online July 1, 2021 https://doi.org/10.3343/alm.2021.41.4.443
Copyright © Korean Society for Laboratory Medicine.
The First Korean Case of NUP98-NSD1 and a Novel SNRK-ETV6 Fusion in a Pediatric Therapy-related Acute Myeloid Leukemia Patient Detected by Targeted RNA Sequencing
Ha Jin Lim, M.D.1* , Jun Hyung Lee, M.D.1* , Young Eun Lee, M.S.1,2 , Hee-Jo Baek, M.D.3 , Hoon Kook, M.D.3 , Ju Heon Park, M.D.1 , Seung Yeob Lee, M.D.1 , Hyun-Woo Choi, M.D.1 , Hyun-Jung Choi, M.D.1 , Seung-Jung Kee, M.D.1 , Jong Hee Shin, M.D.1 , and Myung Geun Shin, M.D.1,2
1Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Korea; 2Brain Korea 21 Plus Project, Chonnam National University Medical School, Gwangju, Korea; 3Department of Pediatrics, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Korea
Correspondence to: Myung-Geun Shin, M.D.
Department of Laboratory Medicine, Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Jeollanam-do 58128, Korea
Tel: +82-61-379-7950, Fax: +82-61-379-7984,
*These authors equally contributed to this study.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Targeted RNA-sequencing (RNA-seq) using next-generation sequencing (NGS) technology is a highly accurate method for selecting and sequencing specific transcripts of interest . We routinely applied a customized targeted RNA-seq system during the diagnostic phase of hematologic malignancies. Our system detected the first Korean case of
In April 2020, a 14-year-old girl visited the outpatient clinic of CNUHH 1.5 years and 1.9 years after a matched unrelated peripheral blood stem cell transplantation and initial diagnosis of AML, respectively, for a follow-up bone marrow (BM) examination At initial diagnosis, the Korean AML 2012 regimen (double-induction strategy with idarubicin or mitoxantrone plus cytarabine, followed by consolidation therapy with cytarabine and etoposide) was administered and complete remission was achieved 28 days after the second induction. The laboratory findings showed a leukocyte count of 3.1×109/L, absolute neutrophil count of 0.58×109/L, hemoglobin of 114 g/L, and platelet count of 37×109/L. BM aspirates revealed 28% leukemic blasts corresponding to French-American-British (FAB) type M2. The BM karyotype was 45,XX,add(3)(p25),del(5)(q?),-12,add(12)(p13)//46,XY, and the multiplex reverse transcription (RT)-PCR (HemaVision kit; DNA Technology, Aarhus, Denmark) finding was negative.
Targeted RNA-seq (HEMEaccuTest RNA; NGeneBio, Seoul, Korea) of the BM sample using STAR-Fusion (ver 1.8.1) and FusionCatcher (ver 1.20) revealed
Figure 1. Schematic representation of the
NUP98-NSD1(A–C) and novel SNRK-ETV6(D–F) gene fusions and proteins. (A) Integrative genomics viewer (IGV) image showing the NUP98-NSD1breakpoints with 171 supporting junction read counts. (B) Direct sequencing confirmed the identical breakpoint causing an in-frame fusion of NUP98-NSD1. (C) The predicted fusion protein translated from the NUP98-NSD1transcript based on a merged sequence produced by STAR-Fusion (ver 1.8.1), which contains domains similar to a previous report  but is shorter. (D) IGV image showing the novel SNRK-ETV6fusion breakpoints with 484 supporting junction read counts. (E) Direct sequencing confirmed the identical breakpoint causing a novel in-frame fusion of SNRK-ETV6. (F) The predicted fusion protein translated from the SNRK-ETV6transcript based on the merged sequence produced by STAR-Fusion (ver 1.8.1).
Compared with previous studies using multiple diagnostic methods to characterize
Lim HJ and Lee JH conceived and designed the study and collected and analyzed the data; Baek HJ and Kook H contributed to the data; Lim HJ and Shin MG wrote the final manuscript; Lee YE, Park JH, Lee SY, Choi HW, Choi HJ, Kee SJ, and Shin JH participated in coordination and discussion. All authors have accepted their responsibility for the entire content of this manuscript and approved the submission.
No potential conflicts of interest relevant to this article were reported.
This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (MSIT) and the Ministry of Health and Welfare (MOHW) (NRF-2019M3E5D1A02067952).
- Zhong Y, Xu F, Wu J, Schubert J, Li MM. Application of next generation sequencing in laboratory medicine. Ann Lab Med 2021; 41: 25-43.
- Hollink IH, van den Heuvel-Eibrink MM, Arentsen-Peters ST, Pratcorona M, Abbas S, Kuipers JE, et al.
NUP98/NSD1characterizes a novel poor prognostic group in acute myeloid leukemia with a distinct HOXgene expression pattern. Blood 2011; 118: 3645-56.
- Niktoreh N, Walter C, Zimmermann M, von Neuhoff C, von Neuhoff N, Rasche M, et al. Mutated
WT1, FLT3-ITD, and NUP98-NSD1fusion in various combinations define a poor prognostic group in pediatric acute myeloid leukemia. J Oncol 2019; 2019: 1609128.
- Franks TM, McCloskey A, Shokirev MN, Benner C, Rathore A, Hetzer MW. Nup98 recruits the Wdr82-Set1A/COMPASS complex to promoters to regulate H3K4 trimethylation in hematopoietic progenitor cells. Genes Dev 2017; 31: 2222-34.
- Li MM, Datto M, Duncavage EJ, Kulkarni S, Lindeman NI, Roy S, et al. Standards and guidelines for the interpretation and reporting of sequence variants in cancer: a joint consensus recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. J Mol Diagn 2017; 19: 4-23.
- Kivioja JL, Thanasopoulou A, Kumar A, Kontro M, Yadav B, Majumder MM, et al. Dasatinib and navitoclax act synergistically to target
NUP98-NSD1(+)/ FLT3-ITD(+) acute myeloid leukemia. Leukemia 2019; 33: 1360-72.
- Mitani Y, Hiwatari M, Seki M, Hangai M, Takita J. Successful treatment of acute myeloid leukemia co-expressing
NUP98/NSD1and FLT3/ITD with preemptive donor lymphocyte infusions. Int J Hematol 2019; 110: 512-6.
- De Braekeleer E, Douet-Guilbert N, Morel F, Le Bris MJ, Basinko A, De Braekeleer M.
ETV6fusion genes in hematological malignancies: a review. Leuk Res 2012; 36: 945-61.
- Kertesz N, Samson J, Debacker C, Wu H, Labastie MC. Cloning and characterization of human and mouse
SNRKsucrose non-fermenting protein (SNF-1)-related kinases. Gene 2002; 294: 13-24.
- Block AW, Carroll AJ, Hagemeijer A, Michaux L, van Lom K, Olney HJ, et al. Rare recurring balanced chromosome abnormalities in therapy-related myelodysplastic syndromes and acute leukemia: report from an international workshop. Genes Chromosomes Cancer 2002; 33: 401-12.