AML with t(16;21)(p11.2;q22)/FUS::ERG rearrangement presenting with hemophagocytes and multinucleated cells: a case report and literature review

AML with t(16;21)(p11.2;q22)/FUS::ERG rearrangement presenting with hemophagocytes and multinucleated cells: a case report and literature review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article AML with t(16;21)(p11.2;q22)/FUS::ERG rearrangement presenting with hemophagocytes and multinucleated cells: a case report and literature review Yingying Chen, Xinhong Yang, Zhihua Zhang, Xiaofeng Yang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8795234/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 10 You are reading this latest preprint version Abstract The FUS :: ERG fusion gene is rare in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), with a predominant prevalence in individuals of Asian descent. The incidence of AML harboring the FUS :: ERG fusion gene is approximately 1%. To date, approximately 154 cases have been reported in the literature. SF3B1 mutation is also rare in AML and frequently coexist with other genetic abnormalities to drive leukemogenesis.In this article,A case of AML harboring t(16;21)(p11.2;q22)/ FUS :: ERG and CSF3R mutations was retrospectively analyzed, with frequent identification of hemophagocytes and multinucleated cells in the bone marrow, and the relevant literature was reviewed. FUS:ERG fusion gene Hemophagocytes Multinucleated cells Acute myeloid leukemia Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction FUS :: ERG (also known as TLS :: ERG ) is a rare chimeric gene generated by the t(16;21)(p11.2;q22) translocation, which was first described by two independent research groups in 1994 [ 1 , 2 ]. The FUS/TLS gene on chromosome 16 is highly homologous to EWSR1 (Ewing sarcoma breakpoint region 1), while the ERG gene on chromosome 21 is associated with erythroid maturation. FUS :: ERG can perturb myeloid and erythroid differentiation, and enhance the proliferation and self-renewal capacities of bone marrow stem and progenitor cells [ 3 ]. The FUS :: ERG fusion gene has been identified in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and a small number of cases of acute lymphoblastic leukemia (ALL) and Ewing sarcoma. Its incidence in AML is less than 1%. It has been reported that AML or MDS patients harboring the FUS :: ERG fusion gene have a poor prognosis, even with allogeneic hematopoietic stem cell transplantation (allo-HSCT)[ 4 ]. The incidence of this fusion gene in ALL is even lower, with only 20 cases reported to date, and the prognosis of these patients is more favorable than that of FUS :: ERG -positive AML patients[ 5 ]. The colony-stimulating factor 3 receptor ( CSF3R ) gene is mapped to chromosome 1p34.3 and consists of 17 exons. It encodes the transmembrane receptor for granulocyte colony-stimulating factor (G-CSF), which transduces proliferative and survival signals to granulocytes and promotes granulocytic differentiation and function [ 6 ]. Herein, we report a case of adult AML with t(16;21)(p11.2;q22)/ FUS :: ERG and CSF3R mutations, and further explore the laboratory features, clinical characteristics, therapeutic strategies and prognosis of this disease through a review of the relevant literature. Case description In December 2023, a previously healthy 51-year-old man was admitted to our hospital because of fever. His hemoglobin level was 74 g/L, white blood cell count 151.40×10 9 /L, platelet count 96 ×10 9 /L and blast cell count 99%. His lactate dehydrogenase level was 1956 U/L.Bone marrow(BM) aspirate smear with 85.5% blasts and immature mononuclear cells. A diagnosis of AML with monocyte leukemia (formally called M5 according to FAB classification) was made (Fig. 1 ). Hemophagocytes, an increased proportion of basophils, as well as binucleated and multinucleated blasts and immature mononuclear cells were observed in the BM(Fig. 2 ).BM flow cytometry analysis revealed approximately 97.07% blasts being positive for CD34, CD 117, CD13, CD33, CD9, CD15(part), CD11b(part), CD56(part);weak for cMPO, CD45, CD38;and no expression of other antigens.BM cytogenetic analysis found abnormal karyotype which is 46,XY, t(8;9) (P23;q22), -16, t(16;21(p11.2;q22),mar 1[ 20 ] (Fig. 3 ). Multiplex-nested reverse transcription-polymerase chain reaction (RT-PCR) was performed for fusion gene screening, and the FUS :: ERG fusion gene was detected (Fig. 4 ).We sequenced the mutational hotspots or whole coding regions of 58 genes that recurrently mutated in hematological malignancies using a amplicon-based Next Generation Sequencing (NGS) protocol with Ion Torrent PGM sequencer (Thermo Fisher Scientific, Waltham, MA, USA) and revealed mutations in CSF3R T618I [VAF (variant allele frequency) 22%)](Fig. 5 ). Treatment and Outcome On admission, the patient received oral hydroxyurea and leukapheresis for leukoreduction, followed by DA induction chemotherapy on December 14, 2023. Cerebrospinal fluid(CSF) flow cytometry on January 2, 2024 detected 25.88% abnormal blasts (CNS leukemia);5 lumbar punctures with intrathecal injection resulted in undetectable CSF blasts and BM complete remission(CR). Consolidation chemotherapy (3 cycles HD-Ara-C, 1 cycle each DA/MA/IA) initiated January 11, 2024 achieved sustained CR by September 18, 2024. During maintenance, BM minimal residual disease(MRD) turned positive (abnormal blasts: 0.44%–1.27%). After declining allo-HSCT, the patient received 2 cycles azacitidine+venetoclax, 1 cycle azacitidine+venetoclax+chidamide. BM re-evaluation April 1, 2025 showed 8.5% blasts/immature mononuclear cells and 12.05% MRD, confirming relapse. Efficacy was unevaluable due to discontinued follow-up/treatment for financial reasons. Discussion with literature review AML is characterized by clonal myeloid blast proliferation in the BM, with approximately 60% of patients harboring chromosomal/genetic aberrations [ 7 ]. The t(16;21)(p11.2;q22) translocation generates the FUS :: ERG fusion gene (16p11 TLS/FUS + 21q22 ERG), which inhibits differentiation and apoptosis via both partner domains [ 8 – 10 ]. Four chimeric transcript types (A-D) are identified in AML, with types B/D encoding the FUS :: ERG protein [ 11 , 12 ]. FUS :: ERG -positive AML frequently co-occurs with karyotypic abnormalities (e.g., + 8, +10, + 16, add(1)(q34), t(8;9), -18)[ 7 ], and the present patient harbored t(8;9)(p23;q22), which may impact prognosis. Epigenetic regulator mutations (RUNX1, TET2, ASXL1, etc.) are also common in this subtype [ 7 ]. FUS :: ERG is rare in MDS,ALL,and Ewing’s tumors, but serves as an independent poor prognostic factor in high-risk AML [ 11 ]. A study of 31 pediatric FUS :: ERG -positive AML patients reported an 87.1% morphological CR rate but a 4-year cumulative incidence of relapse (CIR) of 74% [ 13 ]. The present patient relapsed about 5 months post-CR, consistent with this aggressive phenotype. FUS :: ERG -positive AML is associated with rapid relapse, short event-free survival (EFS), and hematopoietic stem cell transplantation (HSCT) refractoriness [ 4 ], with potential mechanisms including: (1) Loss of major histocompatibility complex (MHC) class I/II and co-stimulatory molecules, linked to EZH2 overexpression (suppressing CIITA); the EZH2 inhibitor tazemetostat may be a potential therapy [ 14 ]. (2) Consistent CD56/CD123 positivity (linked to leukemic stem cell (LSC)-driven chemoresistance); CD123-targeted CAR-T (CART123) shows promise in HSCT recipients [ 15 – 17 ]. The present patient had partial CD56 expression, but CD123 was not tested. (3) Enrichment of PI3K-Akt/MAPK/RTK-RAS pathways and upregulated BCL2 (venetoclax target); combination therapy with pathway inhibitors and/or venetoclax followed by HSCT may improve outcomes [ 18 ]. FUS :: ERG fusion is associated with increased bone or joint pain [ 19 ], and classic morphological features include eosinophilia, increased micromegakaryocytes, hemophagocytes, and vacuolization of leukemic blasts [ 20 ]. Consistent with literature, the present patient showed blast cytoplasmic vacuoles and hemophagocytosis, but lacked eosinophilia and had elevated BM basophils (peak 15%). In there cases of t(16;21)-positive acute basophilic leukemia (ABL) meeting diagnostic criteria, basophilia was observed in PB and BM [ 21 – 23 ]. Notably, multinucleated blasts were frequently observed in BM smears, and these cells exhibited hemophagocytosis. This finding is rarely reported in FUS :: ERG -positive AML and may be associated with dysregulation of the cell cycle and abnormal nuclear division[ 24 ]. The underlying mechanisms require further investigation. The CSF3R gene (1p34.3, exons 14–17) encodes a transmembrane protein promoting granulocyte proliferation and differentiation [ 25 ]. Major mutations include juxtamembrane (predominantly T618I, 68.18%) and cytoplasmic truncating variants [ 25 , 26 ]. CSF3R mutations are highly prevalent in chronic neutrophilic leukemia (CNL, 80–90%) [ 27 ] and occur in 1.6–10.8% of AML [ 28 ], often cooperating with DNA methylation-related gene mutations (53.3%) rather than acting as an independent prognostic factor [ 29 ]. Juxtamembrane mutations activate JAK-STAT signaling (causing leukocytosis), while truncating mutations reduce STAT3:STAT5 activation (increasing bone marrow blasts) [ 27 ]. Targeted therapy data for CSF3R-mutated AML remains limited. In summary, FUS :: ERG is rare in AML, associated with a high relapse rate and poor overall prognosis.CSF3R mutations often co-occur with other genetic alterations to drive leukemogenesis. It is difficult to differentiate this type of AML when hemophagocytes and multinucleated cells are present. A better understanding of the laboratory features of AML cases with FUS :: ERG is needed to aid clinical recognition and optimize therapeutic strategies. Declarations All procedures performed in studies involving human Author contributions All authors collaborated on this research project. XinhongYang conceived and designed the study, and was involved in data acquisition, analysis, and interpretation. Yingying Chen contributed significantly to the data acquisition, analysis, and interpretation. All authors participated in drafting and critically revising the manuscript. They collectively approved the final version for publication and accepted responsibility for all aspects of the work. Funding This research did not receive any dedicated funding from a public, commercial, or not-for-profit agency. Data availability No datasets were generated or analysed during the current study. participants were in accordance with the ethical stan dards of the institutional and/or national research com mittee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Consent for publication Written informed consent for publication was obtained from the patient. Consent to participate Informed consent was obtained from all individual participants included in the study. Competing interests The authors declare no competing interests. References Ichikawa H, Shimizu K, Hayashi Y, et al（1994）An RNA-binding protein gene, TLS/FUS, is fused to ERG in human myeloid leukemia with t(16;21) chromosomal translocation. Cancer Res 54(11):2865-8. Panagopoulos I, Aman P, Fioretos T, et al（1994）Fusion of the FUS gene with ERG in acute myeloid leukemia with t(16;21)(p11;q22). Genes Chromosomes Cancer 11(4):256-62. Heyang Zhang, Qianru Zhan , Xiaoxue Wang ,et al（2022）TLS/FUS‑ERG fusion gene in acute leukemia and myelodysplastic syndrome evolved to acute leukemia: report of six cases and a literature review.Ann Hematol 101(12):2583-2600. Weinberg OK, Porwit A, Orazi A, Hasserjian RP, Foucar K, Duncavage EJ, Arber DA（2023）The International Consensus Classification of acute myeloid leukemia. Virchows Arch 482(1):27-37. Pan J, Zhang Y, Zhao YL, Yang JF, Zhang JP, Liu HX, Wu T, Tong CR（2017）Impact of clinical factors on outcome of leukemia patients with TLS-ERG fusion gene. Leuk Lymphoma 58(7):1655-1663. Metcalf D（1985）The granulocyte-macrophage colony-stimulating factors 43(1):5-6. Zhang H, Zhan Q, Wang X, Gao F, Yu J, Wang J, Fu W, Wang P, Wei X, Zhang L（2022）TLS/FUS-ERG fusion gene in acute leukemia and myelodysplastic syndrome evolved to acute leukemia: report of six cases and a literature review. Ann Hematol 101(12):2583-2600. Crozat A, Aman P, Mandahl N, et al（1993）Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. Nature 17;363(6430):640-4. [9]Prasad DD, Ouchida M, Lee L, et al（1994）TLS/FUS fusion domain of TLS/FUS-erg chimeric protein resulting from the t(16;21) chromosomal translocation in human myeloid leukemia functions as a transcriptional activation domain. Oncogene 9(12):3717-29. Yang L, Embree LJ, Hickstein DD（2000）TLS-ERG leukemia fusion protein inhibits RNA splicing mediated by serine-arginine proteins. Mol Cell Biol 20(10):3345-54. Ichikawa H, Shimizu K, Hayashi Y,et al（1994）An RNA-binding protein gene, TLS/FUS, is fused to ERG in human myeloid leukemia with t(16;21) chromosomal translocation. Cancer Res 54:2865-8 . Kong XT, Ida K, Ichikawa H, et al（1997）Consistent detection of TLS/FUS-ERG chimeric transcripts in acute myeloid leukemia with t(16;21)(p11;q22) and identification of a novel transcript. Blood 90:1192-9. Noort S, Zimmermann M, Reinhardt D,et al（2018）Prognostic impact of t(16;21)(p11;q22) and t(16;21)(q24;q22) in pediatric AML: a retrospective study by the I-BFM study group. Blood 132(15):1584–1592. Buteyn NJ, LaMantia SJ, Burke CG, et al(2025)EZH2-driven immune evasion at disease presentation defines a targetable high-risk subset of acute leukemia exemplified by t(16;21) FUS::ERG AML. bioRxiv [Preprint] 18:2024.05.14.594150. Sun Yao 1, Chen Jianlin 1, Liu Yarong 2,et al(.2019)Donor-Derived CD123-Targeted CAR T Cell Serves as a RIC Regimen for Haploidentical Transplantation in a Patient With FUS-ERG + AML.Front Oncol 3:9:1358. Fan M, Li M, Gao L, Geng S, Wang J, Wang Y, Yan Z, Yu L(2017)Chimeric antigen receptors for adoptive T cell therapy in acute myeloid leukemia. J Hematol Oncol 29;10(1):151. Mu-Mosley H, Ostermann L, Muftuoglu M, Vaidya A, Bonifant CL, Velasquez MP, Gottschalk S, Andreeff M(2022)Transgenic Expression of IL15 Retains CD123-Redirected T Cells in a Less Differentiated State Resulting in Improved Anti-AML Activity in Autologous AML PDX Models. Front Immunol 9;13:880108. Lai A, Liu W, Wei H, Wang Y, Lin D, Zhou C, Liu B, Gu R, Li Y, Wei S, Gong B, Liu K, Gong X, Liu Y, Zhang G, Zhang J, Mi Y, Wang J, Qiu S(2024)The RTK-RAS signaling pathway is enriched in patients with rare acute myeloid leukemia harboring t(16;21)(p11;q22)/ FUS::ERG . Blood Sci 10;6(2):e00188. Jekarl DW, Kim M, Lim J,et al(.2019) CD56 antigen expression and hemophagocytosis of leukemic cells in acute myeloid leukemia with t(16;21)(p11;q22). Front Oncol 3:9:1358. Kong XT, Ida K, Ichikawa H,et al(1997)Consistent detection of TLS/FUS-ERG chimeric transcripts in acute myeloid leukemia with t(16;21)(p11;q22) and identifcation of a novel transcript. Blood 1;90(3):1192-9. Valent, P., K. Sotlar, K. Blatt, K. et al(2017)Proposed diagnostic criteria and classification of basophilic leukemias and related disorders. Leukemia31(4):788-797. Kim, J., T. S. Park, J. Song, K. , et al(2009) Detection of FUS-ERG chimeric transcript in two cases of acute myeloid leukemia with t (16;21)(p11.2;q22) with unusual characteristics. Cancer Genet. Cytogenet. 194:111–118.Cancer Genet Cytogenet 15;194(2):111-8. Yusuke Toda 1, Yuya Nagai 1, Daiki Shimomura ,et al(2017)Acute basophilic leukemia associated with the t(16;21) (p11;q22)/FUS-ERG fusion gene.Clin Case Rep ;5(12):1938-1944. Huang X, Li T, Zhang Y, Gao X, Long F(2023) Hemophagocytosis by multinucleated leukemic blasts, basophilia, and micromegakaryocytes in AML with TLS::ERG. Ann Hematol 102(11):3279-3281. Zhang H, Reister Schultz A, Luty S, et al(2017)Characterization of the leukemogenic potential of distal cytoplasmic CSF3R truncation and missense mutations. Leukemia, 2017, 31(12): 2752-2760.Leukemia 31(12):2752-2760. Vishwanath Anil , Harpreet Gosal , Harsimran Kaur ,et al(2021)Chronic Neutrophilic Leukemia: A Literature Review of the Rare Myeloproliferative Pathology.Cureus 3;13(6):e15433. Ouyang Y, Qiao C, Chen Y, et al(2017)Clinical significance of CSF3R, SRSF2 and SETBP1 mutations in chronic neutrophilic leukemia and chronic myelomonocytic leukemia.Oncotarget 28;8(13):20834-20841. Tarlock K，Alonzo T，Wang YC，et al(2020)Prognostic impact of CSF3R mutations in favorable risk childhood acute myeloid leukemia.Blood 30;135(18):1603-1606. Tarlock K, Alonzo T, Wang YC,et al(2020) Prognostic impact of CSF3R mutations in favorable risk childhood acute myeloid leukemia.Blood 135(18): 1603-1606.Blood. 2020 Apr 30;135(18):1603-1606. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 18 Mar, 2026 Reviews received at journal 16 Mar, 2026 Reviewers agreed at journal 16 Mar, 2026 Reviewers agreed at journal 13 Mar, 2026 Reviews received at journal 11 Mar, 2026 Reviewers agreed at journal 20 Feb, 2026 Reviewers invited by journal 13 Feb, 2026 Editor assigned by journal 12 Feb, 2026 Submission checks completed at journal 12 Feb, 2026 First submitted to journal 05 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8795234","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":591655395,"identity":"47e97ca1-f31a-4979-b79a-fc3203641e86","order_by":0,"name":"Yingying Chen","email":"","orcid":"","institution":"the Affiliated Hospital of Chengde Medical College Chengde","correspondingAuthor":false,"prefix":"","firstName":"Yingying","middleName":"","lastName":"Chen","suffix":""},{"id":591655397,"identity":"8387b9ce-92f6-47a7-9d8b-f4605915b2ed","order_by":1,"name":"Xinhong Yang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5ElEQVRIie3PvYrCQBDA8ZXA2gymHUH3uMZ6IJDWV8kipMpByhQWHpGk8OtVUlomzdqs1ilz+AKxsxA8+xM311nsr54/M8OYZb0h3t81VUtcuP20aoJkbk4GoHtnjAfecK1m1GhlTgRGDkErZFFHk+HP0ulwGBwVIvlyoTVP5IIzN18Fhl+2IcYUet/5RtVyP2Koj4VhS+k/tqhxCqewlpozwi9DgoGPQPdehpEfy8zpkkQeAfHP9SNh3RJQ8ozEPQQ1w0ArMP7ykadl1d64mB7S6nJN5sLNN6+TP+B/45ZlWdZTvyGrS1wv2O42AAAAAElFTkSuQmCC","orcid":"","institution":"the Affiliated Hospital of Chengde Medical College","correspondingAuthor":true,"prefix":"","firstName":"Xinhong","middleName":"","lastName":"Yang","suffix":""},{"id":591655399,"identity":"93ae7bcd-9d10-46a6-80d1-d08347057c0f","order_by":2,"name":"Zhihua Zhang","email":"","orcid":"","institution":"the Affiliated Hospital of Chengde Medical College","correspondingAuthor":false,"prefix":"","firstName":"Zhihua","middleName":"","lastName":"Zhang","suffix":""},{"id":591655405,"identity":"d60ce5cf-a9b9-46d4-aaac-39e03ee7db2d","order_by":3,"name":"Xiaofeng Yang","email":"","orcid":"","institution":"the Affiliated Hospital of Chengde Medical College","correspondingAuthor":false,"prefix":"","firstName":"Xiaofeng","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2026-02-05 09:56:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8795234/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8795234/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102992719,"identity":"87b5e2cf-dca9-4dac-8843-d2d941e59fdb","added_by":"auto","created_at":"2026-02-19 11:41:04","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":589076,"visible":true,"origin":"","legend":"\u003cp\u003eImages of bone marrow aspirate. Blasts and immature mononuclear cells were round, with cytoplasmic vacuoles; the nuclei were round, the chromatin was finely granular, and one or two nucleoli were present per nucleus.(Wright–Giemsa staining × 1000)\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8795234/v1/6135218b0b04d2e8b65e1514.png"},{"id":102992536,"identity":"8cb45333-0db2-4440-b6ed-fe84477dae67","added_by":"auto","created_at":"2026-02-19 11:40:16","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1035310,"visible":true,"origin":"","legend":"\u003cp\u003e2a, 2b, 2c and 2d depict binucleated, trinucleated, tetranucleated and pentanucleated blasts and immature mononuclear cells, respectively; 2e and 2f show hemophagocytes. （Wright-Giemsa stain × 1000）\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8795234/v1/31eba6708e7b8f455e9137d4.png"},{"id":102992609,"identity":"781dc891-a8b6-4285-a8a1-ae4ebf431d8d","added_by":"auto","created_at":"2026-02-19 11:40:38","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":187482,"visible":true,"origin":"","legend":"\u003cp\u003eChromosomal abnormality. The karyotype result was 46,XY, t(8;9) (P23;q22), -16, t(16;21(p11.2;q22),mar 1[20].\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8795234/v1/7cb6391d2d352e0796b68a4d.png"},{"id":102992724,"identity":"0d9b28c9-6349-437c-81bb-006c3cb8fa0b","added_by":"auto","created_at":"2026-02-19 11:41:06","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":35070,"visible":true,"origin":"","legend":"\u003cp\u003eMultiplex-nested PCR analysis of the \u003cem\u003eFUS\u003c/em\u003e::\u003cem\u003eERG\u003c/em\u003e. Lane M1 shows β-actin; Lane R shows transcript of the bone marrow mononuclear cells derived from a normal control; Lane 1d shows the patient. The position and length of the \u003cem\u003eFUS\u003c/em\u003e::\u003cem\u003eERG \u003c/em\u003etranscripts are indicated with a white arrow.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8795234/v1/e6a0ab5f98b24f4ad26948cf.png"},{"id":102992541,"identity":"4b61b0be-a0ab-445e-87d8-3cf677156e42","added_by":"auto","created_at":"2026-02-19 11:40:18","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":144010,"visible":true,"origin":"","legend":"\u003cp\u003eCSF3R mutation was detected using a amplicon-based Next Generation Sequencing (NGS) protocol with Ion Torrent PGM sequencer .(Thermo Fisher Scientific)\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-8795234/v1/9d48dde9716d7490721a3463.png"},{"id":102992760,"identity":"1c4709f7-8d3e-4164-a45c-8b7720dcd240","added_by":"auto","created_at":"2026-02-19 11:41:17","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3174075,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8795234/v1/69ab32f7-b41c-4c04-92d8-12aeb2f7adf7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"AML with t(16;21)(p11.2;q22)/FUS::ERG rearrangement presenting with hemophagocytes and multinucleated cells: a case report and literature review","fulltext":[{"header":"Introduction","content":"\u003cp\u003e \u003cem\u003eFUS\u003c/em\u003e::\u003cem\u003eERG\u003c/em\u003e (also known as \u003cem\u003eTLS\u003c/em\u003e::\u003cem\u003eERG\u003c/em\u003e) is a rare chimeric gene generated by the t(16;21)(p11.2;q22) translocation, which was first described by two independent research groups in 1994 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The \u003cem\u003eFUS/TLS\u003c/em\u003e gene on chromosome 16 is highly homologous to \u003cem\u003eEWSR1\u003c/em\u003e (Ewing sarcoma breakpoint region 1), while the \u003cem\u003eERG\u003c/em\u003e gene on chromosome 21 is associated with erythroid maturation. \u003cem\u003eFUS\u003c/em\u003e::\u003cem\u003eERG\u003c/em\u003e can perturb myeloid and erythroid differentiation, and enhance the proliferation and self-renewal capacities of bone marrow stem and progenitor cells [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The \u003cem\u003eFUS\u003c/em\u003e::\u003cem\u003eERG\u003c/em\u003e fusion gene has been identified in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and a small number of cases of acute lymphoblastic leukemia (ALL) and Ewing sarcoma. Its incidence in AML is less than 1%. It has been reported that AML or MDS patients harboring the \u003cem\u003eFUS\u003c/em\u003e::\u003cem\u003eERG\u003c/em\u003e fusion gene have a poor prognosis, even with allogeneic hematopoietic stem cell transplantation (allo-HSCT)[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The incidence of this fusion gene in ALL is even lower, with only 20 cases reported to date, and the prognosis of these patients is more favorable than that of \u003cem\u003eFUS\u003c/em\u003e::\u003cem\u003eERG\u003c/em\u003e-positive AML patients[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The colony-stimulating factor 3 receptor (\u003cem\u003eCSF3R\u003c/em\u003e) gene is mapped to chromosome 1p34.3 and consists of 17 exons. It encodes the transmembrane receptor for granulocyte colony-stimulating factor (G-CSF), which transduces proliferative and survival signals to granulocytes and promotes granulocytic differentiation and function [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Herein, we report a case of adult AML with t(16;21)(p11.2;q22)/\u003cem\u003eFUS\u003c/em\u003e::\u003cem\u003eERG\u003c/em\u003e and \u003cem\u003eCSF3R\u003c/em\u003e mutations, and further explore the laboratory features, clinical characteristics, therapeutic strategies and prognosis of this disease through a review of the relevant literature.\u003c/p\u003e"},{"header":"Case description","content":"\u003cp\u003eIn December 2023, a previously healthy 51-year-old man was admitted to our hospital because of fever. His hemoglobin level was 74 g/L, white blood cell count 151.40\u0026times;10\u003csup\u003e9\u003c/sup\u003e /L, platelet count 96 \u0026times;10\u003csup\u003e9\u003c/sup\u003e /L and blast cell count 99%. His lactate dehydrogenase level was 1956 U/L.Bone marrow(BM) aspirate smear with 85.5% blasts and immature mononuclear cells. A diagnosis of AML with monocyte leukemia (formally called M5 according to FAB classification) was made (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Hemophagocytes, an increased proportion of basophils, as well as binucleated and multinucleated blasts and immature mononuclear cells were observed in the BM(Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).BM flow cytometry analysis revealed approximately 97.07% blasts being positive for CD34, CD 117, CD13, CD33, CD9, CD15(part), CD11b(part), CD56(part);weak for cMPO, CD45, CD38;and no expression of other antigens.BM cytogenetic analysis found abnormal karyotype which is 46,XY, t(8;9) (P23;q22), -16, t(16;21(p11.2;q22),mar 1[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e20\u003c/span\u003e] (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Multiplex-nested reverse transcription-polymerase chain reaction (RT-PCR) was performed for fusion gene screening, and the \u003cem\u003eFUS\u003c/em\u003e::\u003cem\u003eERG\u003c/em\u003e fusion gene was detected (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).We sequenced the mutational hotspots or whole coding regions of 58 genes that recurrently mutated in hematological malignancies using a amplicon-based Next Generation Sequencing (NGS) protocol with Ion Torrent PGM sequencer (Thermo Fisher Scientific, Waltham, MA, USA) and revealed mutations in CSF3R T618I [VAF (variant allele frequency) 22%)](Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eTreatment and Outcome\u003c/h2\u003e \u003cp\u003eOn admission, the patient received oral hydroxyurea and leukapheresis for leukoreduction, followed by DA induction chemotherapy on December 14, 2023. Cerebrospinal fluid(CSF) flow cytometry on January 2, 2024 detected 25.88% abnormal blasts (CNS leukemia);5 lumbar punctures with intrathecal injection resulted in undetectable CSF blasts and BM complete remission(CR). Consolidation chemotherapy (3 cycles HD-Ara-C, 1 cycle each DA/MA/IA) initiated January 11, 2024 achieved sustained CR by September 18, 2024. During maintenance, BM minimal residual disease(MRD) turned positive (abnormal blasts: 0.44%\u0026ndash;1.27%). After declining allo-HSCT, the patient received 2 cycles azacitidine+venetoclax, 1 cycle azacitidine+venetoclax+chidamide. BM re-evaluation April 1, 2025 showed 8.5% blasts/immature mononuclear cells and 12.05% MRD, confirming relapse. Efficacy was unevaluable due to discontinued follow-up/treatment for financial reasons.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion with literature review","content":"\u003cp\u003eAML is characterized by clonal myeloid blast proliferation in the BM, with approximately 60% of patients harboring chromosomal/genetic aberrations [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The t(16;21)(p11.2;q22) translocation generates the \u003cem\u003eFUS\u003c/em\u003e::\u003cem\u003eERG\u003c/em\u003e fusion gene (16p11 TLS/FUS\u0026thinsp;+\u0026thinsp;21q22 ERG), which inhibits differentiation and apoptosis via both partner domains [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Four chimeric transcript types (A-D) are identified in AML, with types B/D encoding the \u003cem\u003eFUS\u003c/em\u003e::\u003cem\u003eERG\u003c/em\u003e protein [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. \u003cem\u003eFUS\u003c/em\u003e::\u003cem\u003eERG\u003c/em\u003e-positive AML frequently co-occurs with karyotypic abnormalities (e.g., +\u0026thinsp;8, +10, +\u0026thinsp;16, add(1)(q34), t(8;9), -18)[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], and the present patient harbored t(8;9)(p23;q22), which may impact prognosis. Epigenetic regulator mutations (RUNX1, TET2, ASXL1, etc.) are also common in this subtype [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cem\u003eFUS\u003c/em\u003e::\u003cem\u003eERG\u003c/em\u003e is rare in MDS,ALL,and Ewing\u0026rsquo;s tumors, but serves as an independent poor prognostic factor in high-risk AML [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. A study of 31 pediatric \u003cem\u003eFUS\u003c/em\u003e::\u003cem\u003eERG\u003c/em\u003e-positive AML patients reported an 87.1% morphological CR rate but a 4-year cumulative incidence of relapse (CIR) of 74% [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The present patient relapsed about 5 months post-CR, consistent with this aggressive phenotype. \u003cem\u003eFUS\u003c/em\u003e::\u003cem\u003eERG\u003c/em\u003e-positive AML is associated with rapid relapse, short event-free survival (EFS), and hematopoietic stem cell transplantation (HSCT) refractoriness [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], with potential mechanisms including: (1) Loss of major histocompatibility complex (MHC) class I/II and co-stimulatory molecules, linked to EZH2 overexpression (suppressing CIITA); the EZH2 inhibitor tazemetostat may be a potential therapy [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. (2) Consistent CD56/CD123 positivity (linked to leukemic stem cell (LSC)-driven chemoresistance); CD123-targeted CAR-T (CART123) shows promise in HSCT recipients [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR14\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The present patient had partial CD56 expression, but CD123 was not tested. (3) Enrichment of PI3K-Akt/MAPK/RTK-RAS pathways and upregulated BCL2 (venetoclax target); combination therapy with pathway inhibitors and/or venetoclax followed by HSCT may improve outcomes [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cem\u003eFUS\u003c/em\u003e::\u003cem\u003eERG\u003c/em\u003e fusion is associated with increased bone or joint pain [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e19\u003c/span\u003e], and classic morphological features include eosinophilia, increased micromegakaryocytes, hemophagocytes, and vacuolization of leukemic blasts [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Consistent with literature, the present patient showed blast cytoplasmic vacuoles and hemophagocytosis, but lacked eosinophilia and had elevated BM basophils (peak 15%). In there cases of t(16;21)-positive acute basophilic leukemia (ABL) meeting diagnostic criteria, basophilia was observed in PB and BM [\u003cspan additionalcitationids=\"CR22\" citationid=\"CR20\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Notably, multinucleated blasts were frequently observed in BM smears, and these cells exhibited hemophagocytosis. This finding is rarely reported in \u003cem\u003eFUS\u003c/em\u003e::\u003cem\u003eERG\u003c/em\u003e-positive AML and may be associated with dysregulation of the cell cycle and abnormal nuclear division[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The underlying mechanisms require further investigation.\u003c/p\u003e \u003cp\u003eThe \u003cem\u003eCSF3R\u003c/em\u003e gene (1p34.3, exons 14\u0026ndash;17) encodes a transmembrane protein promoting granulocyte proliferation and differentiation [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Major mutations include juxtamembrane (predominantly T618I, 68.18%) and cytoplasmic truncating variants [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. \u003cem\u003eCSF3R\u003c/em\u003e mutations are highly prevalent in chronic neutrophilic leukemia (CNL, 80\u0026ndash;90%) [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e27\u003c/span\u003e] and occur in 1.6\u0026ndash;10.8% of AML [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e28\u003c/span\u003e], often cooperating with DNA methylation-related gene mutations (53.3%) rather than acting as an independent prognostic factor [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Juxtamembrane mutations activate JAK-STAT signaling (causing leukocytosis), while truncating mutations reduce STAT3:STAT5 activation (increasing bone marrow blasts) [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Targeted therapy data for CSF3R-mutated AML remains limited.\u003c/p\u003e \u003cp\u003eIn summary, \u003cem\u003eFUS\u003c/em\u003e::\u003cem\u003eERG\u003c/em\u003e is rare in AML, associated with a high relapse rate and poor overall prognosis.CSF3R mutations often co-occur with other genetic alterations to drive leukemogenesis. It is difficult to differentiate this type of AML when hemophagocytes and multinucleated cells are present. A better understanding of the laboratory features of AML cases with \u003cem\u003eFUS\u003c/em\u003e::\u003cem\u003eERG\u003c/em\u003e is needed to aid clinical recognition and optimize therapeutic strategies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAll procedures performed in studies involving human\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003eAll authors collaborated on this research project. XinhongYang conceived and designed the study, and was involved in data acquisition, analysis, and interpretation. Yingying Chen contributed significantly to the data acquisition, analysis, and interpretation. All authors participated in drafting and critically revising the manuscript. They collectively approved the final version for publication and accepted responsibility for all aspects of the work.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003eThis research did not receive any dedicated funding from a public, commercial, or not-for-profit agency.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003eNo datasets were generated or analysed during the current study.\u003c/p\u003e\n\u003cp\u003eparticipants were in accordance with the ethical stan dards of the institutional and/or national research com mittee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003eWritten informed consent for publication was obtained from the patient.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u0026nbsp;\u003c/strong\u003eInformed consent was obtained from all individual participants included in the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eIchikawa H, Shimizu K, Hayashi Y, et al（1994）An RNA-binding protein gene, TLS/FUS, is fused to ERG in human myeloid leukemia with t(16;21) chromosomal translocation. Cancer Res 54(11):2865-8.\u003c/li\u003e\n \u003cli\u003ePanagopoulos I, Aman P, Fioretos T, et al（1994）Fusion of the FUS gene with ERG in acute myeloid leukemia with t(16;21)(p11;q22). Genes Chromosomes Cancer 11(4):256-62.\u003c/li\u003e\n \u003cli\u003eHeyang Zhang, Qianru Zhan , Xiaoxue Wang ,et al（2022）TLS/FUS‑ERG fusion gene in acute leukemia and myelodysplastic syndrome evolved to acute leukemia: report of six cases and a literature review.Ann Hematol 101(12):2583-2600.\u003c/li\u003e\n \u003cli\u003eWeinberg OK, Porwit A, Orazi A, Hasserjian RP, Foucar K, Duncavage EJ, Arber DA（2023）The International Consensus Classification of acute myeloid leukemia. Virchows Arch 482(1):27-37.\u003c/li\u003e\n \u003cli\u003ePan J, Zhang Y, Zhao YL, Yang JF, Zhang JP, Liu HX, Wu T, Tong CR（2017）Impact of clinical factors on outcome of leukemia patients with TLS-ERG fusion gene. Leuk Lymphoma 58(7):1655-1663.\u003c/li\u003e\n \u003cli\u003eMetcalf D（1985）The granulocyte-macrophage colony-stimulating factors 43(1):5-6.\u003c/li\u003e\n \u003cli\u003eZhang H, Zhan Q, Wang X, Gao F, Yu J, Wang J, Fu W, Wang P, Wei X, Zhang L（2022）TLS/FUS-ERG fusion gene in acute leukemia and myelodysplastic syndrome evolved to acute leukemia: report of six cases and a literature review. Ann Hematol 101(12):2583-2600.\u003c/li\u003e\n \u003cli\u003eCrozat A, Aman P, Mandahl N, et al（1993）Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. Nature 17;363(6430):640-4. [9]Prasad DD, Ouchida M, Lee L, et al（1994）TLS/FUS fusion domain of TLS/FUS-erg chimeric protein resulting from the t(16;21) chromosomal translocation in human myeloid leukemia functions as a transcriptional activation domain. Oncogene 9(12):3717-29.\u003c/li\u003e\n \u003cli\u003eYang L, Embree LJ, Hickstein DD（2000）TLS-ERG leukemia fusion protein inhibits RNA splicing mediated by serine-arginine proteins. Mol Cell Biol 20(10):3345-54.\u003c/li\u003e\n \u003cli\u003eIchikawa H, Shimizu K, Hayashi Y,et al（1994）An RNA-binding protein gene, TLS/FUS, is fused to ERG in human myeloid leukemia with t(16;21) chromosomal translocation. Cancer Res 54:2865-8\u003cstrong\u003e.\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003eKong XT, Ida K, Ichikawa H, et al（1997）Consistent detection of TLS/FUS-ERG chimeric transcripts in acute myeloid leukemia with t(16;21)(p11;q22) and identification of a novel transcript. Blood 90:1192-9.\u003c/li\u003e\n \u003cli\u003eNoort S, Zimmermann M, Reinhardt D,et al（2018）Prognostic impact of t(16;21)(p11;q22) and t(16;21)(q24;q22) in pediatric AML: a retrospective study by the I-BFM study group. Blood 132(15):1584\u0026ndash;1592.\u003c/li\u003e\n \u003cli\u003eButeyn NJ, LaMantia SJ, Burke CG, et al(2025)EZH2-driven immune evasion at disease presentation defines a targetable high-risk subset of acute leukemia exemplified by t(16;21) FUS::ERG AML. bioRxiv [Preprint] 18:2024.05.14.594150.\u003c/li\u003e\n \u003cli\u003eSun Yao 1, Chen Jianlin 1, Liu Yarong 2,et al(.2019)Donor-Derived CD123-Targeted CAR T Cell Serves as a RIC Regimen for Haploidentical Transplantation in a Patient With \u003cem\u003eFUS-ERG\u003c/em\u003e+ AML.Front Oncol 3:9:1358.\u003c/li\u003e\n \u003cli\u003eFan M, Li M, Gao L, Geng S, Wang J, Wang Y, Yan Z, Yu L(2017)Chimeric antigen receptors for adoptive T cell therapy in acute myeloid leukemia. 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Front Oncol 3:9:1358.\u003c/li\u003e\n \u003cli\u003eKong XT, Ida K, Ichikawa H,et al(1997)Consistent detection of TLS/FUS-ERG chimeric transcripts in acute myeloid leukemia with t(16;21)(p11;q22) and identifcation of a novel transcript. Blood 1;90(3):1192-9.\u003c/li\u003e\n \u003cli\u003eValent, P., K. Sotlar, K. Blatt, K. et al(2017)Proposed diagnostic criteria and classification of basophilic leukemias and related disorders. Leukemia31(4):788-797.\u003c/li\u003e\n \u003cli\u003eKim, J., T. S. Park, J. Song, K. , et al(2009) Detection of FUS-ERG chimeric transcript in two cases of acute myeloid leukemia with t (16;21)(p11.2;q22) with unusual characteristics. Cancer Genet. Cytogenet. 194:111\u0026ndash;118.Cancer Genet Cytogenet 15;194(2):111-8.\u003c/li\u003e\n \u003cli\u003eYusuke Toda 1, Yuya Nagai 1, Daiki Shimomura ,et al(2017)Acute basophilic leukemia associated with the t(16;21) (p11;q22)/FUS-ERG fusion gene.Clin Case Rep\u003c/li\u003e\n \u003cli\u003e;5(12):1938-1944.\u003c/li\u003e\n \u003cli\u003eHuang X, Li T, Zhang Y, Gao X, Long F(2023) Hemophagocytosis by multinucleated leukemic blasts, basophilia, and micromegakaryocytes in AML with TLS::ERG. Ann Hematol 102(11):3279-3281.\u003c/li\u003e\n \u003cli\u003eZhang H, Reister Schultz A, Luty S, et al(2017)Characterization of the leukemogenic potential of distal cytoplasmic CSF3R truncation and missense mutations. Leukemia, 2017, 31(12): 2752-2760.Leukemia 31(12):2752-2760.\u003c/li\u003e\n \u003cli\u003eVishwanath Anil , Harpreet Gosal , Harsimran Kaur ,et al(2021)Chronic Neutrophilic Leukemia: A Literature Review of the Rare Myeloproliferative Pathology.Cureus 3;13(6):e15433.\u003c/li\u003e\n \u003cli\u003eOuyang Y, Qiao C, Chen Y, et al(2017)Clinical significance of CSF3R, SRSF2 and SETBP1 mutations in chronic neutrophilic leukemia and chronic myelomonocytic leukemia.Oncotarget 28;8(13):20834-20841.\u003c/li\u003e\n \u003cli\u003eTarlock K，Alonzo T，Wang YC，et al(2020)Prognostic impact of CSF3R mutations in favorable risk childhood acute myeloid leukemia.Blood 30;135(18):1603-1606.\u003c/li\u003e\n \u003cli\u003eTarlock K, Alonzo T, Wang YC,et al(2020) Prognostic impact of CSF3R mutations in favorable risk childhood acute myeloid leukemia.Blood 135(18): 1603-1606.Blood. 2020 Apr 30;135(18):1603-1606.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"annals-of-hematology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aohe","sideBox":"Learn more about [Annals of Hematology](http://link.springer.com/journal/277)","snPcode":"277","submissionUrl":"https://submission.nature.com/new-submission/277/3","title":"Annals of Hematology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"FUS:ERG fusion gene, Hemophagocytes, Multinucleated cells, Acute myeloid leukemia","lastPublishedDoi":"10.21203/rs.3.rs-8795234/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8795234/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe \u003cem\u003eFUS\u003c/em\u003e::\u003cem\u003eERG\u003c/em\u003efusion gene is rare in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), with a predominant prevalence in individuals of Asian descent. The incidence of AML harboring the \u003cem\u003eFUS\u003c/em\u003e::\u003cem\u003eERG\u003c/em\u003efusion gene is approximately 1%. To date, approximately 154 cases have been reported in the literature.\u003cem\u003eSF3B1\u003c/em\u003e mutation is also rare in AML and frequently coexist with other genetic abnormalities to drive leukemogenesis.In this article,A case of AML harboring t(16;21)(p11.2;q22)/\u003cem\u003eFUS\u003c/em\u003e::\u003cem\u003eERG\u003c/em\u003e and \u003cem\u003eCSF3R\u003c/em\u003emutations was retrospectively analyzed, with frequent identification of hemophagocytes and multinucleated cells in the bone marrow, and the relevant literature was reviewed.\u003c/p\u003e","manuscriptTitle":"AML with t(16;21)(p11.2;q22)/FUS::ERG rearrangement presenting with hemophagocytes and multinucleated cells: a case report and literature review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-19 11:38:39","doi":"10.21203/rs.3.rs-8795234/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-18T12:45:23+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-16T13:57:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"214204270966542070344024645943050424905","date":"2026-03-16T12:48:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"221401543444714010768080600126208190998","date":"2026-03-13T18:05:57+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-11T21:52:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"267180853689593474080976916126404130876","date":"2026-02-20T07:32:26+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-13T14:39:28+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-12T13:55:34+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-12T13:53:54+00:00","index":"","fulltext":""},{"type":"submitted","content":"Annals of Hematology","date":"2026-02-05T09:22:23+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"annals-of-hematology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aohe","sideBox":"Learn more about [Annals of Hematology](http://link.springer.com/journal/277)","snPcode":"277","submissionUrl":"https://submission.nature.com/new-submission/277/3","title":"Annals of Hematology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"f2b7d556-706c-4123-a761-71196a8b8261","owner":[],"postedDate":"February 19th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-05-05T13:39:56+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-19 11:38:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8795234","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8795234","identity":"rs-8795234","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}