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The 2013 seminal discovery of oncogenic driver mutations in colony\u2010stimulating factor 3 receptor (\n                      <jats:italic>CSF3R<\/jats:italic>\n                      ) in the majority of patients with CNL not only established its molecular pathogenesis but provided a diagnostic biomarker and rationale for pharmacological targeting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Diagnosis<\/jats:title>\n                    <jats:p>\n                      In 2016, the World Health Organization (WHO) recognized activating\n                      <jats:italic>CSF3R<\/jats:italic>\n                      mutations as a central diagnostic feature of CNL. Other criteria include leukocytosis of \u226525\u2009\u00d7\u200910\n                      <jats:sup>9<\/jats:sup>\n                      \/L comprising &gt;80% neutrophils with &lt;10% circulating precursors and rare blasts, and absence of dysplasia or monocytosis, while not fulfilling criteria for other MPN.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Management<\/jats:title>\n                    <jats:p>There is currently no standard of care for management of CNL, due in large part to the rarity of disease and dearth of formal clinical trials. Most commonly used therapeutic agents include conventional oral chemotherapy (e.g., hydroxyurea), interferon, and Janus kinase (JAK) inhibitors, while hematopoietic stem cell transplant remains the only potentially curative modality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Disease Updates<\/jats:title>\n                    <jats:p>Increasingly comprehensive genetic profiling in CNL, including new data on clonal evolution, has disclosed a complex genomic landscape with additional mutations and combinations thereof driving disease progression and drug resistance. Although accurate prognostic stratification and therapeutic decision\u2010making remain challenging in CNL, emerging data on molecular biomarkers and the addition of newer agents, such as JAK inhibitors, to the therapeutic arsenal, are paving the way toward greater standardization and improvement of patient care.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ajh.26481","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T09:35:11Z","timestamp":1643362511000},"page":"491-505","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Chronic neutrophilic leukemia: 2022 update on diagnosis, genomic landscape, prognosis, and management"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1499-6171","authenticated-orcid":false,"given":"Natasha","family":"Szuber","sequence":"first","affiliation":[{"name":"Department of Hematology Maisonneuve\u2010Rosemont Hospital  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7366-9886","authenticated-orcid":false,"given":"Michelle","family":"Elliott","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4605-3821","authenticated-orcid":false,"given":"Ayalew","family":"Tefferi","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000441-192007000-00003"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(64)92142-7"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1999.17.12.3835"},{"key":"e_1_2_8_5_1","volume-title":"World Health Organization Classification of Tumours: Pathology and Genetics of Tumours and Lymphoid Tissue","author":"Jaffe ES","year":"2001"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1996.7082329.x"},{"key":"e_1_2_8_7_1","unstructured":"SEER Hematopoietic and Lymphoid Neoplasm Database Chronic Neutrophilic Leukemia. 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