Ahmed Mohamed , Juehua Gao , Yi-Hua Chen , Yasmin Abaza , Jessica Altman , Lawrence Jennings , Erica Vormittag-Nocito , Madina Sukhanova , Xinyan Lu , Qing Chen
{"title":"CSF3R突变的髓系肿瘤:超越慢性中性粒细胞白血病。","authors":"Ahmed Mohamed , Juehua Gao , Yi-Hua Chen , Yasmin Abaza , Jessica Altman , Lawrence Jennings , Erica Vormittag-Nocito , Madina Sukhanova , Xinyan Lu , Qing Chen","doi":"10.1016/j.humpath.2024.06.008","DOIUrl":null,"url":null,"abstract":"<div><p><em>CSF3R</em> activating mutation is a genetic hallmark of chronic neutrophilic leukemia (CNL), and is also present in a subset of atypical chronic myeloid leukemia (aCML), but infrequent in other myeloid neoplasms. However, the occurrence of <em>CSF3R</em> mutations in various myeloid neoplasms is not well studied. Here we evaluate the spectrum of CSF3R mutations and the clinicopathologic features of <em>CSF3R</em> mutated myeloid neoplasms. We retrospectively identified <em>CSF3R</em> mutations in a variety of myeloid neoplasms: two CNL, three atypical chronic myeloid leukemia (aCML), nine acute myeloid leukemia (AML), one chronic myelomonocytic leukemia, and one myeloproliferative neoplasm. The prototypic T618I mutation was found in 50% of cases: CNL (2/2), aCML (2/3) and AML (4/9). We observed a new recurrent <em>CSF3R</em> mutation Q776* in 25% of cases, and a potential-germline mutation in a 20-year-old patient. Co-occurring mutations were often in epigenetic modifier and spliceosome. <em>IDH/RUNX1</em> and tumor suppressor mutations were frequent in AML but absent in CNL/aCML. All CNL/aCML patients succumbed within 2-years of diagnosis. We demonstrate that <em>CSF3R</em> mutations are not restricted to CNL. CNL and aCML show similar clinicopathologic and molecular features, suggesting that CNL may be best classified as myelodysplastic/myeloproliferative neoplasm rather than myeloproliferative neoplasm.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"CSF3R mutated myeloid neoplasms: Beyond chronic neutrophilic leukemia\",\"authors\":\"Ahmed Mohamed , Juehua Gao , Yi-Hua Chen , Yasmin Abaza , Jessica Altman , Lawrence Jennings , Erica Vormittag-Nocito , Madina Sukhanova , Xinyan Lu , Qing Chen\",\"doi\":\"10.1016/j.humpath.2024.06.008\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><em>CSF3R</em> activating mutation is a genetic hallmark of chronic neutrophilic leukemia (CNL), and is also present in a subset of atypical chronic myeloid leukemia (aCML), but infrequent in other myeloid neoplasms. However, the occurrence of <em>CSF3R</em> mutations in various myeloid neoplasms is not well studied. Here we evaluate the spectrum of CSF3R mutations and the clinicopathologic features of <em>CSF3R</em> mutated myeloid neoplasms. We retrospectively identified <em>CSF3R</em> mutations in a variety of myeloid neoplasms: two CNL, three atypical chronic myeloid leukemia (aCML), nine acute myeloid leukemia (AML), one chronic myelomonocytic leukemia, and one myeloproliferative neoplasm. The prototypic T618I mutation was found in 50% of cases: CNL (2/2), aCML (2/3) and AML (4/9). We observed a new recurrent <em>CSF3R</em> mutation Q776* in 25% of cases, and a potential-germline mutation in a 20-year-old patient. Co-occurring mutations were often in epigenetic modifier and spliceosome. <em>IDH/RUNX1</em> and tumor suppressor mutations were frequent in AML but absent in CNL/aCML. All CNL/aCML patients succumbed within 2-years of diagnosis. We demonstrate that <em>CSF3R</em> mutations are not restricted to CNL. CNL and aCML show similar clinicopathologic and molecular features, suggesting that CNL may be best classified as myelodysplastic/myeloproliferative neoplasm rather than myeloproliferative neoplasm.</p></div>\",\"PeriodicalId\":13062,\"journal\":{\"name\":\"Human pathology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2024-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Human pathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0046817724001096\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PATHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human pathology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0046817724001096","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PATHOLOGY","Score":null,"Total":0}
CSF3R activating mutation is a genetic hallmark of chronic neutrophilic leukemia (CNL), and is also present in a subset of atypical chronic myeloid leukemia (aCML), but infrequent in other myeloid neoplasms. However, the occurrence of CSF3R mutations in various myeloid neoplasms is not well studied. Here we evaluate the spectrum of CSF3R mutations and the clinicopathologic features of CSF3R mutated myeloid neoplasms. We retrospectively identified CSF3R mutations in a variety of myeloid neoplasms: two CNL, three atypical chronic myeloid leukemia (aCML), nine acute myeloid leukemia (AML), one chronic myelomonocytic leukemia, and one myeloproliferative neoplasm. The prototypic T618I mutation was found in 50% of cases: CNL (2/2), aCML (2/3) and AML (4/9). We observed a new recurrent CSF3R mutation Q776* in 25% of cases, and a potential-germline mutation in a 20-year-old patient. Co-occurring mutations were often in epigenetic modifier and spliceosome. IDH/RUNX1 and tumor suppressor mutations were frequent in AML but absent in CNL/aCML. All CNL/aCML patients succumbed within 2-years of diagnosis. We demonstrate that CSF3R mutations are not restricted to CNL. CNL and aCML show similar clinicopathologic and molecular features, suggesting that CNL may be best classified as myelodysplastic/myeloproliferative neoplasm rather than myeloproliferative neoplasm.
期刊介绍:
Human Pathology is designed to bring information of clinicopathologic significance to human disease to the laboratory and clinical physician. It presents information drawn from morphologic and clinical laboratory studies with direct relevance to the understanding of human diseases. Papers published concern morphologic and clinicopathologic observations, reviews of diseases, analyses of problems in pathology, significant collections of case material and advances in concepts or techniques of value in the analysis and diagnosis of disease. Theoretical and experimental pathology and molecular biology pertinent to human disease are included. This critical journal is well illustrated with exceptional reproductions of photomicrographs and microscopic anatomy.