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While several common subtypes are well characterized, hairy cell leukemia (HCL) remains incompletely understood. This review frames HCL within mature B-cell neoplasms, emphasizing tumor microenvironment-driven interactions and the immunoregulatory roles of extracellular vesicles in disease pathogenesis.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/understanding-hairy-cell-leukemia-in-the-context-of-mature-bcell-neoplasms-tumor-microenvironment-and-extracellular-vesicle-contribution-to-disease-pathogenesis/352514/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/understanding-hairy-cell-leukemia-in-the-context-of-mature-bcell-neoplasms-tumor-microenvironment-and-extracellular-vesicle-contribution-to-disease-pathogenesis/352514.png","ImageObject",300,407,{"name":92,"@type":93},"Genevieve","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-27","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is hairy cell leukemia (HCL) considered less understood compared with other mature B-cell neoplasms?","Question",{"text":112,"@type":113},"The document states that rare mature B-cell neoplasms, including HCL, remain poorly understood due to limited patient sample availability and restricted access to preclinical models.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What role does the tumor microenvironment (TME) play in mature B-cell neoplasms and HCL?",{"text":117,"@type":113},"It describes TME as a pivotal contributor to initiation and progression across malignancies, and highlights ongoing challenges in understanding interactions such as immune invasion, stromal crosstalk, and tissue remodeling in rare diseases like HCL.",{"name":119,"@type":110,"acceptedAnswer":120},"How do extracellular vesicles (EVs) contribute to disease pathogenesis in this review?",{"text":121,"@type":113},"EVs are presented as central mediators of intercellular communication that influence disease progression, immune modulation, and treatment response by delivering bioactive cargo and engaging immune and non-immune TME components, including stromal cells.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},352514,1790492920,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},1374391974585,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","TYPE Review  \nPUBLISHED 18 February 2026  \nDOI 10.3389/fimmu.2026.1741794  \nOPEN ACCESS  \nEDITED BY  \nMichele Costanzo,  \nUniversity of Naples Federico II, Italy  \nREVIEWED BY  \nWilliam Sewell,  \nUniversity of New South Wales, Australia Xavier Troussard,  \nCentre Hospitalier Universitaire de Caen, France  \n*CORRESPONDENCE  \nChiara Ciardiello  \n [c.ciardiello@istitutotumori. na.it](c.ciardiello@istitutotumori. na.it)[ ](c.ciardiello@istitutotumori. na.it)Lucia Catani  \n [lucia.catani@unibo.it](lucia.catani@unibo.it)  \n†These authors have contributed equally to this work  \nRECEIVED 07 November 2025  \nREVISED 05 January 2026  \nACCEPTED 26 January 2026  \nPUBLISHED 18 February 2026  \nCITATION  \nIngangi V, Amoroso D, Passaro E, Di Vaia V, Maltoni F, Narimanfar G, Minopoli M, Rosa R, Ametrano M, Di Gennaro E, Broccoli A, Zinzani PL, Catani L and Ciardiello C (2026)  \nUnderstanding hairy cell leukemia in the context of mature B−cell neoplasms: tumor microenvironment and extracellular vesicle contribution to disease pathogenesis.  \nFront. Immunol. 17:1741794 .  \ndoi: 10.3389/fimmu.2026.1741794  \nCOPYRIGHT  \n© 2026 Ingangi, Amoroso, Passaro, Di Vaia, Maltoni, Narimanfar, Minopoli, Rosa, Ametrano, Di Gennaro, Broccoli, Zinzani, Catani and Ciardiello. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nUnderstanding hairy cell leukemia in the context of mature B−cell neoplasms:  \ntumor microenvironment and extracellular vesicle contribution to disease pathogenesis  \nVincenzo Ingangi 1†, Dominga Amoroso 1†, Eugenia Passaro 2, Vincenzo Di Vaia 1, Filippo Maltoni 3, Ghazal Narimanfar 4, Michele Minopoli 1, Rita Rosa 2, Mariateresa Ametrano 1,  \nElena Di Gennaro 2, Alessandro Broccoli 3,4, Pier Luigi Zinzani 3,4, Lucia Catani 3,4* and Chiara Ciardiello 1*  \n1 Preclinical Models of Tumor Progression Unit- Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy, 2 Experimental Pharmacology Unit, Istituto Nazionale Tumori –IRCCS– Fondazione G. Pascale, Naples, Italy, 3 IRCCS Azienda Ospedaliero-Universitaria di Bologna, Institute of Hematology “ L. e A. Seràgnoli”, Bologna, Italy, 4 Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy  \nMature B-cell neoplasms constitute a biologically and clinically heterogeneous group of hematologic malignancies, defined by the clonal proliferation and accumulation of monotypic mature B lymphocytes, which may involve the peripheral blood, bone marrow (BM), lymphoid tissues, or present primarily in extranodal sites. While the pathogenesis of common subtypes, such as chronic lymphocytic leukemia, multiple myeloma, Hodgkin Lymphoma and Diffuse Large B-cell Lymphoma has been extensively studied, those of rare entities like Hairy Cell Leukemia (HCL) remains poorly understood. HCL is a distinct B-cell neoplasm marked by BM infiltration of atypical “hairy” cells, pancytopenia, BM fibrosis, and the BRAF V600E mutation, which is a defining molecular hallmark of the classic form of the disease. Analogous to solid tumors, growing evidence shows that the tumor microenvironment (TME) is a pivotal contributor in both the initiation and progression of all these malignancies. However, in rare mature B-cell neoplasms, understanding how tumor cells interact with their microenvironment, in terms of immune invasion, stromal crosstalk, and tissue remodeling, remains a challenge, partly due to the scarcity of patient samples and limited availability of preclinical models. In the context of TME, extracellular vesicles (EVs) have emerged as central mediators of intercellular communication within both so","cbCaikZ6kbmtonMx","https://ap.wps.com/l/cbCaikZ6kbmtonMx","pdf",2845819,18,"English","# 1 Epidemiological trends and classification of mature B-cell neoplasms\n## Mature B-cell neoplasms overview\n## Hairy cell leukemia as a rare entity\n## Tumor microenvironment and extracellular vesicles in pathogenesis","[{\"question\":\"Why is hairy cell leukemia (HCL) considered less understood compared with other mature B-cell neoplasms?\",\"answer\":\"The document states that rare mature B-cell neoplasms, including HCL, remain poorly understood due to limited patient sample availability and restricted access to preclinical models.\"},{\"question\":\"What role does the tumor microenvironment (TME) play in mature B-cell neoplasms and HCL?\",\"answer\":\"It describes TME as a pivotal contributor to initiation and progression across malignancies, and highlights ongoing challenges in understanding interactions such as immune invasion, stromal crosstalk, and tissue remodeling in rare diseases like HCL.\"},{\"question\":\"How do extracellular vesicles (EVs) contribute to disease pathogenesis in this review?\",\"answer\":\"EVs are presented as central mediators of intercellular communication that influence disease progression, immune modulation, and treatment response by delivering bioactive cargo and engaging immune and non-immune TME components, including stromal cells.\"}]","Understanding hairy cell leukemia in the context of mature B−cell neoplasms: tumor microenvironment and extracellular vesicle contribution to disease pathogenesis | PDF",1790100066,45]