{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:52:52Z","timestamp":1789015972270,"version":"build-2803163510"},"reference-count":99,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T00:00:00Z","timestamp":1666656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Clonal expansions of large granular lymphocytes (LGL) have been reported in a wide spectrum of conditions, with LGL leukemia (LGLL) being the most extreme. However, the boundaries between LGLL and LGL clones are often subtle, and both conditions can be detected in several clinical scenarios, particularly in patients with cytopenias. The intricate overlap of LGL clonal expansion with other disease entities characterized by unexplained cytopenias makes their classification challenging. Indeed, precisely assigning whether cytopenias might be related to inadequate hematopoiesis (i.e., LGL as a marginal finding) rather than immune-mediated mechanisms (i.e., LGLL) is far from being an easy task. As LGL clones acquire different pathogenetic roles and relevance according to their diverse clinical settings, their detection in the landscape of bone marrow failures and myeloid neoplasms has recently raised growing clinical interest. In this regard, the current availability of different diagnostic techniques, including next generation sequencing, shed light on the relationship between LGL clones and cytopenias, paving the way towards a better disease classification for precision medicine treatments. Herein, we discuss the clinical relevance of LGL clones in the diagnostic algorithm to be followed in patients presenting with cytopenias, offering a foundation for rational management approaches.<\/jats:p>","DOI":"10.3390\/cancers14215236","type":"journal-article","created":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T12:29:45Z","timestamp":1666700985000},"page":"5236","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["LGL Clonal Expansion and Unexplained Cytopenia: Two Clues Don\u2019t Make an Evidence"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8646-2932","authenticated-orcid":false,"given":"Giulia","family":"Calabretto","sequence":"first","affiliation":[{"name":"Department of Medicine, Padua University School of Medicine, Hematology Division, 35129 Padua, Italy"},{"name":"Veneto Institute of Molecular Medicine (VIMM), 35129 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Attardi","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6829-5544","authenticated-orcid":false,"given":"Carmelo","family":"Gurnari","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy"},{"name":"Translational Hematology and Oncology Research Department, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianpietro","family":"Semenzato","sequence":"additional","affiliation":[{"name":"Department of Medicine, Padua University School of Medicine, Hematology Division, 35129 Padua, Italy"},{"name":"Veneto Institute of Molecular Medicine (VIMM), 35129 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6164-4761","authenticated-orcid":false,"given":"Maria Teresa","family":"Voso","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8799-5324","authenticated-orcid":false,"given":"Renato","family":"Zambello","sequence":"additional","affiliation":[{"name":"Department of Medicine, Padua University School of Medicine, Hematology Division, 35129 Padua, Italy"},{"name":"Veneto Institute of Molecular Medicine (VIMM), 35129 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1182\/blood-2016-08-692590","article-title":"LGL Leukemia: From Pathogenesis to Treatment","volume":"129","author":"Lamy","year":"2017","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zawit, M., Bahaj, W., Gurnari, C., and Maciejewski, J. 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