{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T23:55:12Z","timestamp":1783814112636,"version":"3.55.0"},"reference-count":65,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T00:00:00Z","timestamp":1600387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Atypical chronic myeloid leukemia, BCR-ABL1 negative (aCML) is a rare myelodysplastic syndrome (MDS)\/myeloproliferative neoplasm (MPN) with a high rate of transformation to acute myeloid leukemia, and poor survival. Until now, the diagnosis has been based on morphological grounds only, possibly making the real frequency of the disease underestimated. Only recently, new insights in the molecular biology of MDS\/MPN syndromes have deepened our knowledge of aCML, enabling us to have a better molecular profile of the disease. The knowledge gleaned from next generation sequencing has complemented morphologic and laboratory WHO criteria for myeloid neoplasms and can provide greater specificity in distinguishing aCML from alternative MDS\/MPN or MPNs. The most commonly mutated genes (&gt;20%) in aCML are SETBP1, ASXL1, N\/K-RAS, SRSF2, and TET2, and less frequently (&lt; 10%) CBL, CSFR3, JAK2, EZH2, and ETNK1. Several of these mutations affect the JAK-STAT, MAPK, and ROCK signaling pathways, which are targetable by inhibitors that are already in clinical use and may lead to a personalized treatment of aCML patients unfit for allogeneic transplant, which is currently the only curative option for fit patients. In this review, we present two emblematic clinical cases and address the new molecular findings in aCML and the available treatment options.<\/jats:p>","DOI":"10.3390\/ijms21186862","type":"journal-article","created":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T10:22:23Z","timestamp":1600424543000},"page":"6862","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Atypical Chronic Myeloid Leukemia: Where Are We Now?"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1912-0574","authenticated-orcid":false,"given":"Elena","family":"Cris\u00e0","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carit\u00e0, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maura","family":"Nicolosi","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carit\u00e0, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Ferri","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carit\u00e0, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Favini","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carit\u00e0, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4681-0151","authenticated-orcid":false,"given":"Gianluca","family":"Gaidano","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carit\u00e0, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Patriarca","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carit\u00e0, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1182\/blood-2014-06-579466","article-title":"Recurrent ETNK1 mutations in atypical chronic myeloid leukemia","volume":"125","author":"Donadoni","year":"2015","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1002\/ajh.24722","article-title":"Targeted next generation sequencing and identification of risk factors in World Health Organization defined atypical chronic myeloid leukemia","volume":"92","author":"Patnaik","year":"2017","journal-title":"Am. 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