{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:35:55Z","timestamp":1790516155080,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,10]],"date-time":"2022-04-10T00:00:00Z","timestamp":1649548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CHU CAEN","award":["ARPI2017"],"award-info":[{"award-number":["ARPI2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Hairy cell leukemia (cHCL) patients have, in most cases, a specific clinical and biological presentation with splenomegaly, anemia, leukopenia, neutropenia, monocytopenia and\/or thrombocytopenia, identification of hairy cells that express CD103, CD123, CD25, CD11c and identification of the V600E mutation in the B-Raf proto-oncogene (BRAF) in 90% of cases. Monocytopenia is absent in vHCL and SDRPL patients and the abnormal cells do not express CD25 or CD123 and do not present the BRAFV600E mutation. Ten percent of cHCL patients are BRAFWT and the distinction between cHCL and HCL-like disorders including the variant form of HCL (vHCL) and splenic diffuse red pulp lymphoma (SDRPL) can be challenging. We performed deep sequencing in a large cohort of 84 cHCL and 16 HCL-like disorders to improve insights into the pathogenesis of the diseases. BRAF mutations were detected in 76\/82 patients of cHCL (93%) and additional mutations were identified in Kr\u00fcppel-like Factor 2 (KLF2) in 19 patients (23%) or CDKN1B in 6 patients (7.5%). Some KLF2 genetic alterations were localized on the cytidine deaminase (AID) consensus motif, suggesting AID-induced mutations. When analyzing sequential samples, a clonal evolution was identified in half of the cHCL patients (6\/12 pts). Among the 16 patients with HCL-like disorders, we observed an enrichment of MAP2K1 mutations in vHCL\/SDRPL (3\/5 pts) and genes involved in the epigenetic regulation (KDM6A, EZH2, CREBBP, ARID1A) (3\/5 pts). Furthermore, MAP2K1 mutations were associated with a bad prognosis and a shorter time to next treatment (TTNT) and progression-free survival (PFS), independently of the HCL classification.<\/jats:p>","DOI":"10.3390\/cancers14081904","type":"journal-article","created":{"date-parts":[[2022,4,10]],"date-time":"2022-04-10T06:02:54Z","timestamp":1649570574000},"page":"1904","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Deciphering Genetic Alterations of Hairy Cell Leukemia and Hairy Cell Leukemia-like Disorders in 98 Patients"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5967-8225","authenticated-orcid":false,"given":"Elsa","family":"Maitre","sequence":"first","affiliation":[{"name":"INSERM U1245, Normandie University, UNIROUEN, UNICAEN, 14032 Caen, France"},{"name":"Laboratory of Hematology, University Hospital Caen, Avenue de la C\u00f4te de Nacre, CEDEX, 14033 Caen, France"},{"name":"Structure F\u00e9d\u00e9rative SF-MOCAE, University Hospital Caen, Avenue de la C\u00f4te de Nacre, CEDEX, 14033 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4093-6463","authenticated-orcid":false,"given":"C\u00e9cile","family":"Tomowiak","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Hospital Poitiers, 2 rue Mil\u00e9trie, 86000 Poitiers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4890-336X","authenticated-orcid":false,"given":"Benjamin","family":"Lebecque","sequence":"additional","affiliation":[{"name":"Laboratory Hematology, University Hospital Clermont-Ferrand, 58 rue Montalembert, 63000 Clermont-Ferrrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6768-7175","authenticated-orcid":false,"given":"Fontanet","family":"Bijou","sequence":"additional","affiliation":[{"name":"Department of Hematology, Institut Bergoni\u00e9, 229 Cours de l\u2019Argonne, CEDEX, 33079 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled","family":"Benabed","sequence":"additional","affiliation":[{"name":"Department of Hematology, Centre Hospitalier Public du Cotentin, 46 rue du Val de Saire, 50100 Cherbourg-en-Cotentin, France"},{"name":"Department of Hematology, Centre Henri Becquerel, 1 rue d\u2019Amiens, CEDEX, 76038 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8914-4814","authenticated-orcid":false,"given":"Dina","family":"Naguib","sequence":"additional","affiliation":[{"name":"Laboratory of Hematology, University Hospital Caen, Avenue de la C\u00f4te de Nacre, CEDEX, 14033 Caen, France"},{"name":"Structure F\u00e9d\u00e9rative SF-MOCAE, University Hospital Caen, Avenue de la C\u00f4te de Nacre, CEDEX, 14033 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Kerneves","sequence":"additional","affiliation":[{"name":"Laboratory of Hematology, University Hospital Caen, Avenue de la C\u00f4te de Nacre, CEDEX, 14033 Caen, France"},{"name":"Structure F\u00e9d\u00e9rative SF-MOCAE, University Hospital Caen, Avenue de la C\u00f4te de Nacre, CEDEX, 14033 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1667-3421","authenticated-orcid":false,"given":"Edouard","family":"Cornet","sequence":"additional","affiliation":[{"name":"INSERM U1245, Normandie University, UNIROUEN, UNICAEN, 14032 Caen, France"},{"name":"Laboratory of Hematology, University Hospital Caen, Avenue de la C\u00f4te de Nacre, CEDEX, 14033 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9636-8971","authenticated-orcid":false,"given":"Pierre-Julien","family":"Viailly","sequence":"additional","affiliation":[{"name":"INSERM U1245, Normandie University, UNIROUEN, UNICAEN, 14032 Caen, France"},{"name":"Department of Hematology, Centre Henri Becquerel, 1 rue d\u2019Amiens, CEDEX, 76038 Rouen, France"},{"name":"Hematology Institute, University Hospital Caen, Avenue de la C\u00f4te de Nacre, 14033 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Arsham","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Hospital Poitiers, 2 rue Mil\u00e9trie, 86000 Poitiers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7278-9651","authenticated-orcid":false,"given":"Brigitte","family":"Sola","sequence":"additional","affiliation":[{"name":"INSERM U1245, Normandie University, UNIROUEN, UNICAEN, 14032 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Jardin","sequence":"additional","affiliation":[{"name":"INSERM U1245, Normandie University, UNIROUEN, UNICAEN, 14032 Caen, France"},{"name":"Department of Hematology, Centre Henri Becquerel, 1 rue d\u2019Amiens, CEDEX, 76038 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Troussard","sequence":"additional","affiliation":[{"name":"INSERM U1245, Normandie University, UNIROUEN, UNICAEN, 14032 Caen, France"},{"name":"Laboratory of Hematology, University Hospital Caen, Avenue de la C\u00f4te de Nacre, CEDEX, 14033 Caen, France"},{"name":"Hematology Institute, University Hospital Caen, Avenue de la C\u00f4te de Nacre, 14033 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"443","DOI":"10.3322\/caac.21357","article-title":"2016 US lymphoid malignancy statistics by World Health Organization subtypes: 2016 US Lymphoid Malignancy Statistics by World Health Organization Subtypes","volume":"66","author":"Teras","year":"2016","journal-title":"CA Cancer J. 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