{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:05:25Z","timestamp":1791345925851,"version":"4.3.1"},"reference-count":51,"publisher":"American Society of Hematology","issue":"14","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,10,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The incidence and prognosis of clonal hematopoiesis in patients with isolated neutropenia among patients with idiopathic cytopenia of undetermined significance (ICUS), known as ICUS-N or chronic idiopathic neutropenia (CIN) patients, is poorly defined. The current study sought to investigate the frequency and clinical significance of mutations of genes implicated in myeloid malignancies using next-generation sequencing in patients with CIN (n = 185) with a long follow-up. We found that 21 (11.35%) of 185 patients carried a total of 25 somatic mutations in 6 genes with a median variant allele frequency of 12.75%. The most frequently mutated genes were DNMT3A and TET2 involving &amp;gt;80% of patients, followed by IDH1\/2, SRSF2, and ZRSR2. The frequency of transformation to a myeloid malignancy was low in the total group of patients (5 of 185 patients [2.70%]). However, from the transformed patients, 4 belonged to the clonal group (4 of 21 [19.05%]) and 1 to the nonclonal group (1 of 164 [0.61%]), indicating that the presence of mutation(s) confers a relative risk for transformation of 31.24 (P = .0017). The variant allele frequency of the mutant clones in the transformed patients was &amp;gt;10% in all cases, and the genes most frequently associated with malignant transformation were SRSF2 and IDH1. No significant differences were identified between the clonal and nonclonal groups in the severity of neutropenia. Patients with clonal disease were older compared with nonclonal patients. These data contribute to the better understanding of the heterogeneous entities underlying ICUS and highlight the importance of mutation analysis for the diagnosis and prognosis of patients with unexplained neutropenias.<\/jats:p>","DOI":"10.1182\/blood.2021010815","type":"journal-article","created":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T03:08:15Z","timestamp":1625108895000},"page":"1249-1257","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":28,"title":["Incidence and prognosis of clonal hematopoiesis in patients with chronic idiopathic neutropenia"],"prefix":"10.1182","volume":"138","author":[{"given":"Grigorios","family":"Tsaknakis","sequence":"first","affiliation":[{"name":"Hemopoiesis Research Laboratory, School of Medicine, University of Crete\u2013Department of Hematology, University Hospital of Heraklion, Heraklion, Greece;"},{"name":"Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research and Technology-Hellas (FORTH), Heraklion, Greece;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4039-3756","authenticated-orcid":false,"given":"Anna","family":"Gall\u00ec","sequence":"additional","affiliation":[{"name":"Department of Hematology Oncology, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2635-7441","authenticated-orcid":false,"given":"Stavros","family":"Papadakis","sequence":"additional","affiliation":[{"name":"Hemopoiesis Research Laboratory, School of Medicine, University of Crete\u2013Department of Hematology, University Hospital of Heraklion, Heraklion, Greece;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy","family":"Kanellou","sequence":"additional","affiliation":[{"name":"Department of Hematology, Venizeleion General Hospital, Heraklion, Greece;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0058-7142","authenticated-orcid":false,"given":"Chiara","family":"Elena","sequence":"additional","affiliation":[{"name":"Department of Hematology Oncology, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6583-3829","authenticated-orcid":false,"given":"Gabriele","family":"Todisco","sequence":"additional","affiliation":[{"name":"Department of Hematology Oncology, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy;"},{"name":"Department of Molecular Medicine, University of Pavia, Pavia, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Bono","sequence":"additional","affiliation":[{"name":"Department of Hematology Oncology, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy;"},{"name":"Department of Molecular Medicine, University of Pavia, 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Greece;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7395-7896","authenticated-orcid":false,"given":"Irene","family":"Mavroudi","sequence":"additional","affiliation":[{"name":"Hemopoiesis Research Laboratory, School of Medicine, University of Crete\u2013Department of Hematology, University Hospital of Heraklion, Heraklion, Greece;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charalampos","family":"Pontikoglou","sequence":"additional","affiliation":[{"name":"Hemopoiesis Research Laboratory, School of Medicine, University of Crete\u2013Department of Hematology, University Hospital of Heraklion, Heraklion, Greece;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4030-1209","authenticated-orcid":false,"given":"Anastasios","family":"Batas","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research and Technology-Hellas (FORTH), Heraklion, Greece;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9676-3720","authenticated-orcid":false,"given":"Stella","family":"Maxouri","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research and Technology-Hellas (FORTH), Heraklion, Greece;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanouela","family":"Linardaki","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research and Technology-Hellas (FORTH), Heraklion, Greece;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5253-1466","authenticated-orcid":false,"given":"Nektarios","family":"Tavernarakis","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research and 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