{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:04:08Z","timestamp":1791489848345,"version":"4.3.4"},"reference-count":98,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T00:00:00Z","timestamp":1690502400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"R.A.W.","doi-asserted-by":"publisher","award":["R37CA233476"],"award-info":[{"award-number":["R37CA233476"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"R.A.W.","doi-asserted-by":"publisher","award":["R01CA236722"],"award-info":[{"award-number":["R01CA236722"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"R.A.W.","doi-asserted-by":"publisher","award":["R01CA265929"],"award-info":[{"award-number":["R01CA265929"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive neoplasm of mature T-cells. Most patients with T-PLL present with lymphocytosis, anemia, thrombocytopenia, and hepatosplenomegaly. Correct identification of T-PLL is essential because treatment for this disease is distinct from that of other T-cell neoplasms. In 2019, the T-PLL International Study Group (TPLL-ISG) established criteria for the diagnosis, staging, and assessment of response to treatment of T-PLL with the goal of harmonizing research efforts and supporting clinical decision-making. T-PLL pathogenesis is commonly driven by T-cell leukemia 1 (TCL1) overexpression and ATM loss, genetic alterations that are incorporated into the TPLL-ISG diagnostic criteria. The cooperativity between TCL1 family members and ATM is seemingly unique to T-PLL across the spectrum of T-cell neoplasms. The role of the T-cell receptor, its downstream kinases, and JAK\/STAT signaling are also emerging themes in disease pathogenesis and have obvious therapeutic implications. Despite improved understanding of disease pathogenesis, alemtuzumab remains the frontline therapy in the treatment of na\u00efve patients with indications for treatment given its high response rate. Unfortunately, the responses achieved are rarely durable, and the majority of patients are not candidates for consolidation with hematopoietic stem cell transplantation. Improved understanding of T-PLL pathogenesis has unveiled novel therapeutic vulnerabilities that may change the natural history of this lymphoproliferative neoplasm and will be the focus of this concise review.<\/jats:p>","DOI":"10.3390\/ijms241512106","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T07:35:24Z","timestamp":1690529724000},"page":"12106","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["T-Cell Prolymphocytic Leukemia: Diagnosis, Pathogenesis, and Treatment"],"prefix":"10.3390","volume":"24","author":[{"given":"Marc","family":"Gutierrez","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Bladek","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Illinois Chicago, Chicago, IL 60607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Busra","family":"Goksu","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Illinois Chicago, Chicago, IL 60607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2238-5066","authenticated-orcid":false,"given":"Carlos","family":"Murga-Zamalloa","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Illinois Chicago, Chicago, IL 60607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale","family":"Bixby","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI 60607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6420-0760","authenticated-orcid":false,"given":"Ryan","family":"Wilcox","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI 60607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/S0140-6736(73)93135-8","article-title":"Prolymphocytic Leukaemia of B and T Cell Type","volume":"2","author":"Catovsky","year":"1973","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1182\/blood-2004-01-0002","article-title":"A Systematic Approach to Diagnosis of Mature T-Cell Leukemias Reveals Heterogeneity among WHO Categories","volume":"104","author":"Herling","year":"2004","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1182\/blood.2019000402","article-title":"Consensus Criteria for Diagnosis, Staging, and Treatment Response Assessment of T-Cell Prolymphocytic Leukemia","volume":"134","author":"Staber","year":"2019","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1182\/blood.2022015851","article-title":"The International Consensus Classification of Mature Lymphoid Neoplasms: A Report from the Clinical Advisory Committee","volume":"140","author":"Campo","year":"2022","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1038\/s41375-022-01620-2","article-title":"The 5th Edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms","volume":"36","author":"Alaggio","year":"2022","journal-title":"Leukemia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3269","DOI":"10.1182\/blood.V78.12.3269.3269","article-title":"Clinical and Laboratory Features of 78 Cases of T-Prolymphocytic Leukemia","volume":"78","author":"Matutes","year":"1991","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1182\/blood.V86.3.1163.1163","article-title":"True T-Cell Chronic Lymphocytic Leukemia: A Morphologic and Immunophenotypic Study of 25 Cases","volume":"86","author":"Hoyer","year":"1995","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1046\/j.1365-2141.1998.00977.x","article-title":"Indolent Course as a Relatively Frequent Presentation in T-Prolymphocytic Leukaemia. 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