{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:52:41Z","timestamp":1789015961603,"version":"build-2803163510"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T00:00:00Z","timestamp":1682640000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T00:00:00Z","timestamp":1682640000000},"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":["Exp Hematol Oncol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Isolated chronic idiopathic neutropenia (CIN) is a rare disease with multiple contributing etiologies that must be ruled out before establishing a diagnosis. We studied clinical and molecular data of 238 consecutive adult patients with CIN. Autoimmune neutropenia was present in 28% of our cohort. In contrast, T cell-mediated neutropenia was the main underlying pathological mechanism among patients with T cell expansions, such as T-cell large granular lymphocytic leukemia (T-LGL) and T cell clonopathy of undetermined significance, found in 37% and 8% of cases, respectively. Patients with neutropenia also had hypogammaglobulinemia (6%) and\/or monoclonal gammopathy of undetermined significance (5%). NGS application has further broadened the spectrum of causes of CIN by including manifestations of clonal hematopoiesis, present in 12% of cases. <jats:italic>TET2<\/jats:italic> (3%), <jats:italic>TP53<\/jats:italic> (2%), and <jats:italic>IDH1\/IDH2<\/jats:italic> (2%) mutations were the most commonly found and were enriched in cases with T-LGL. We show that these clinico-molecular associations can be simultaneously present, complicating a proper diagnostic distinction within the broader entity of seemingly idiopathic neutropenia of autoimmune origin. Identification of etiologic culprits may also guide rational selection of therapies.<\/jats:p>","DOI":"10.1186\/s40164-023-00403-4","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T14:02:42Z","timestamp":1682690562000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["New approaches to idiopathic neutropenia in the era of clonal hematopoiesis"],"prefix":"10.1186","volume":"12","author":[{"given":"Olisaemeka D.","family":"Ogbue","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tariq","family":"Kewan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waled S.","family":"Bahaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmelo","family":"Gurnari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Visconte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaroslaw P.","family":"Maciejewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,4,28]]},"reference":[{"key":"403_CR1","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1182\/blood-2015-03-634493","volume":"126","author":"F Sicre de Fontbrune","year":"2015","unstructured":"Sicre de Fontbrune F, Moignet A, Beaupain B, et al. Severe chronic primary neutropenia in adults: report on a series of 108 patients. Blood. 2015;126:1643\u201350.","journal-title":"Blood"},{"key":"403_CR2","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.3324\/haematol.2009.018481","volume":"95","author":"B Bareau","year":"2010","unstructured":"Bareau B, Rey J, Hamidou M, et al. Analysis of a French cohort of patients with large granular lymphocyte leukemia: a report on 229 cases. Haematologica. 2010;95:1534\u201341.","journal-title":"Haematologica"},{"key":"403_CR3","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.1182\/blood.V84.5.1620.1620","volume":"84","author":"MV Dhodapkar","year":"1994","unstructured":"Dhodapkar MV, Li CY, Lust JA, Tefferi A, Phyliky RL. Clinical spectrum of clonal proliferations of T-large granular lymphocytes: a T-cell clonopathy of undetermined significance? 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Exp Hematol. 2008;36:293\u2013300.","journal-title":"Exp Hematol"},{"key":"403_CR6","doi-asserted-by":"publisher","first-page":"4418","DOI":"10.3390\/cancers13174418","volume":"13","author":"M Zawit","year":"2021","unstructured":"Zawit M, Bahaj W, Gurnari C, Maciejewski J. Large granular lymphocytic leukemia: from immunopathogenesis to treatment of refractory disease. Cancers. 2021;13:4418.","journal-title":"Cancers"},{"key":"403_CR7","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1182\/blood.2021010815","volume":"138","author":"G Tsaknakis","year":"2021","unstructured":"Tsaknakis G, Galli A, Papadakis S, et al. Incidence and prognosis of clonal hematopoiesis in patients with chronic idiopathic neutropenia. Blood. 2021;138:1249\u201357.","journal-title":"Blood"},{"issue":"18","key":"403_CR8","doi-asserted-by":"publisher","first-page":"317","DOI":"10.3238\/arztebl.2016.0317","volume":"113","author":"M Heuser","year":"2016","unstructured":"Heuser M, Thol F, Ganser A. clonal hematopoiesis of indeterminate potential. Dtsch Arztebl Int. 2016;113(18):317\u201322. https:\/\/doi.org\/10.3238\/arztebl.2016.0317.","journal-title":"Dtsch Arztebl Int"},{"key":"403_CR9","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.3390\/cancers14051340","volume":"14","author":"C Bravo-Perez","year":"2022","unstructured":"Bravo-Perez C, Carrillo-Tornel S, Garcia-Torralba E, Jerez A. Persistent large granular lymphocyte clonal expansions: \u201cthe root of many evils\u201d-and of some goodness. Cancers. 2022;14:1340.","journal-title":"Cancers."},{"key":"403_CR10","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1080\/10428194.2017.1339880","volume":"59","author":"SR Sanikommu","year":"2018","unstructured":"Sanikommu SR, Clemente MJ, Chomczynski P, et al. Clinical features and treatment outcomes in large granular lymphocytic leukemia (LGLL). Leuk Lymphoma. 2018;59:416\u201322.","journal-title":"Leuk Lymphoma"}],"container-title":["Experimental Hematology &amp; Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40164-023-00403-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40164-023-00403-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40164-023-00403-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T14:05:58Z","timestamp":1682690758000},"score":1,"resource":{"primary":{"URL":"https:\/\/ehoonline.biomedcentral.com\/articles\/10.1186\/s40164-023-00403-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,28]]},"references-count":10,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["403"],"URL":"https:\/\/doi.org\/10.1186\/s40164-023-00403-4","relation":{},"ISSN":["2162-3619"],"issn-type":[{"value":"2162-3619","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,28]]},"assertion":[{"value":"11 April 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 April 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 April 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was conducted at Cleveland Clinic Foundation, OH following approval by the Institutional Review Board. Consent was obtained from patients and all data was de-identified in accordance with HIPPA regulations.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"The authors declare no competing financial interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"42"}}