{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T12:27:33Z","timestamp":1762432053696},"reference-count":8,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T00:00:00Z","timestamp":1617667200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T00:00:00Z","timestamp":1617667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Hematol"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic neutrophilic leukemia (CNL) is a rare but serious myeloid malignancy. In a review of reported cases for WHO-defined CNL, CSF3R mutation is found in about 90% cases and confirmed as the molecular basis of CNL. Concurrent mutations are observed in CSF3R-mutated CNL patients, including ASXL1, SETBP1, SRSF2, JAK2, CALR, TET2, NRAS, U2AF1, and CBL. Both ASXL1 and SETBP1 mutations in CNL have been associated with a poor prognosis, whereas, SRSF2 mutation was undetermined. Our patient was a 77-year-old man and had no significant past medical history and symptoms with leukocytosis. Bone marrow (BM) aspirate and biopsy revealed a markedly hypercellular marrow with prominent left-shifted granulopoiesis. Next-generation sequencing (NGS) of DNA from the BM aspirate of a panel of 28 genes, known to be pathogenic in MDS\/MPN, detected mutations in CSF3R, SETBP1, and SRSF2, and a diagnosis of CNL was made. The patient did not use a JAK-STAT pathway inhibitor (ruxolitinib) but started on hydroxyurea and alpha-interferon and developed pruritus after 4 months of diagnosis and nasal hemorrhage 1 month later. Then, the patient was diagnosed with CNL with AML transformation and developed intracranial hemorrhage and died. We repeated NGS and found that three additional mutations were detected: ASXL1, PRKDC, MYOM2; variant allele frequency (VAF) of the prior mutations in CSF3R, SETBP1, and SRSF2 increased. The concurrence of CSF3RT618I, ASXL1, SETBP1, and SRSF2 mutation may be a mutationally detrimental combination and contribute to disease progression and AML transformation, as well as the nonspecific treatment of hydroxyurea and alpha-interferon, but the significance and role of PRKDC and MYOM2 mutations were not undetermined.<\/jats:p>","DOI":"10.1007\/s00277-021-04491-2","type":"journal-article","created":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T07:02:31Z","timestamp":1617692551000},"page":"1459-1461","update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["CSF3R T618I, SETBP1 G870S, SRSF2 P95H, and ASXL1 Q780* tetramutation co-contribute to myeloblast transformation in a chronic neutrophilic leukemia"],"prefix":"10.1007","volume":"100","author":[{"given":"Yi","family":"Qian","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoming","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,4,6]]},"reference":[{"issue":"9","key":"4491_CR1","doi-asserted-by":"publisher","first-page":"1870","DOI":"10.1038\/leu.2013.122","volume":"27","author":"A Pardanani","year":"2013","unstructured":"Pardanani A, Lasho TL, Laborde RR, Elliott M, Hanson CA, Knudson RA, Ketterling RP, Maxson JE, Tyner JW, Tefferi A (2013) CSF3R T618I is a highly prevalent and specific mutation in chronic neutrophilic leukemia. Leukemia. 27(9):1870\u20131873","journal-title":"Leukemia."},{"issue":"7","key":"4491_CR2","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1002\/ajh.24031","volume":"90","author":"MA Elliott","year":"2015","unstructured":"Elliott MA, Pardanani A, Hanson CA, Lasho TL, Finke CM, Belachew AA, Tefferi A (2015) ASXL1 mutations are frequent and prognostically detrimental in CSF3R-mutated chronic neutrophilic leukemia. Am J Hematol 90(7):653\u2013656","journal-title":"Am J Hematol"},{"key":"4491_CR3","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/s13045-014-0077-1","volume":"7","author":"Y Cui","year":"2014","unstructured":"Cui Y, Li B, Gale RP, Jiang Q, Xu Z, Qin T, Zhang P, Zhang Y, Xiao Z (2014) CSF3R, SETBP1 and CALR mutations in chronic neutrophilic leukemia. J Hematol Oncol 7:77","journal-title":"J Hematol Oncol"},{"issue":"1","key":"4491_CR4","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.bbrc.2019.12.030","volume":"523","author":"A Price","year":"2020","unstructured":"Price A, Druhan LJ, Lance A, Clark G, Vestal CG, Zhang Q, Foureau D, Parsons J, Hamilton A, Steuerwald NM, Avalos BR (2020) T618I CSF3R mutations in chronic neutrophilic leukemia induce oncogenic signals through aberrant trafficking and constitutive phosphorylation of the O-glycosylated receptor form. Biochem Biophys Res Commun 523(1):208\u2013213","journal-title":"Biochem Biophys Res Commun"},{"issue":"6","key":"4491_CR5","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1182\/blood-2016-10-695981","volume":"129","author":"JE Maxson","year":"2017","unstructured":"Maxson JE, Tyner JW (2017) Genomics of chronic neutrophilic leukemia. Blood. 129(6):715\u2013722","journal-title":"Blood."},{"issue":"16","key":"4491_CR6","doi-asserted-by":"publisher","first-page":"3329","DOI":"10.1002\/cncr.31586","volume":"124","author":"Y Zhang","year":"2018","unstructured":"Zhang Y, Wang F, Chen X, Zhang Y, Wang M, Liu H, Cao P, Ma X, Wang T, Zhang J, Zhang X, Lu P, Liu H (2018) CSF3R mutations are frequently associated with abnormalities of RUNX1, CBFB, CEBPA, and NPM1 genes in acute myeloid leukemia. Cancer. 124(16):3329\u20133338","journal-title":"Cancer."},{"issue":"1","key":"4491_CR7","first-page":"82","volume":"28","author":"YJ Guo","year":"2020","unstructured":"Guo YJ, Wang Y, Wang LH, Zuo YB, Niu ZY, Lin FR, Zhang JY (2020) Analysis of clinical features and prognosis of patients with chronic neutrophil leukemia. Zhongguo Shi Yan Xue Ye Xue Za Zhi 28(1):82\u201387","journal-title":"Zhongguo Shi Yan Xue Ye Xue Za Zhi"},{"issue":"10","key":"4491_CR8","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1080\/10245332.2018.1471794","volume":"23","author":"JP Arbab","year":"2018","unstructured":"Arbab JP, Ayatollahi H, Sadeghi R, Sheikhi M, Asghari A (2018) Prognostic significance of SRSF2 mutations in myelodysplastic syndromes and chronic myelomonocytic leukemia: a meta-analysis. Hematology. 23(10):778\u2013784","journal-title":"Hematology."}],"container-title":["Annals of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-021-04491-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00277-021-04491-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-021-04491-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T06:18:01Z","timestamp":1620800281000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00277-021-04491-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,6]]},"references-count":8,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["4491"],"URL":"https:\/\/doi.org\/10.1007\/s00277-021-04491-2","relation":{},"ISSN":["0939-5555","1432-0584"],"issn-type":[{"value":"0939-5555","type":"print"},{"value":"1432-0584","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,6]]},"assertion":[{"value":"24 October 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 March 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 April 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Written informed consent was obtained from the patient for the publication of this case report and any accompanying images.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}