[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-360680-105":59,"doc-detail-360680-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","immunomodulatory-role-of-megakaryocytes-in-the-hematopoietic-niche-of-myeloproliferative-neoplasms-research","Immunomodulatory role of megakaryocytes in the hematopoietic niche of myeloproliferative neoplasms - Research","","Myeloproliferative neoplasms (MPN) are clonal stem cell disorders marked by dysregulated megakaryopoiesis and expansion of neoplastic hematopoietic stem cells. Megakaryocytes (MK) regulate HSC function and shape marrow immune responses. Using an aged murine MPN model with MK-restricted JAK2V617F expression, mutant MK show stronger antigen uptake and MHC I presentation, increased pro-inflammatory cytokines, and T-cell dysregulation. Enhanced MK immune activity associates with mutant clone expansion and MPN development, while single-cell RNA sequencing shows aging amplifies JAK2V617F MK-driven immune remodeling and LINE-1 activation. Human data confirm LINE-1–encoded ORF1p in MK from most MPN patients.",{"@graph":69,"@context":123},[70,84,106],{"@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/immunomodulatory-role-of-megakaryocytes-in-the-hematopoietic-niche-of-myeloproliferative-neoplasms-research/360680/",{"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/immunomodulatory-role-of-megakaryocytes-in-the-hematopoietic-niche-of-myeloproliferative-neoplasms-research/360680.png","ImageObject",300,407,{"name":92,"@type":93},"Kurz","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",14,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What role do megakaryocytes play in the hematopoietic niche of MPN?","Question",{"text":113,"@type":114},"Megakaryocytes regulate hematopoietic stem cell functions and shape immune responses within the marrow niche, influencing both steady-state and stress hematopoiesis.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How was JAK2V617F-related mutant megakaryocyte immunomodulation studied?",{"text":118,"@type":114},"The study used an aging murine MPN model with MK-restricted JAK2V617F expression and compared mutant MK with wild-type MK, including chimeric models and single-cell RNA sequencing.",{"name":120,"@type":111,"acceptedAnswer":121},"What molecular changes connect aging, mutant MK, and marrow inflammation?",{"text":122,"@type":114},"Aging amplified JAK2V617F MK-driven immune remodeling and was associated with increased LINE-1 retrotransposon transcripts, elevated cGAS/STING innate immune sensors, and niche inflammation.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},360680,1790218147,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":105,"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},2336478945635,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","ARTICLE-Myeloproliferative Disorders  \nImmunomodulatory role of megakaryocytes in the hematopoietic niche of myeloproliferative neoplasms  \nXiaoxi Yang,1,2* Sandy Lee,3* Kyla Masarik,1 Tameena Ahmed,4 Lei Zheng5 and Huichun Zhan1,6  \n1 Department of Medicine, Stony Brook School of Medicine, Stony Brook, NY, USA; 2 Division of Rheumatology, Peking Union Medical College Hospital, Beijing, China; 3The Graduate Program in Molecular & Cellular Biology, Stony Brook University, Stony Brook, NY, USA; 4 Department of Pathology, Stony Brook University, Stony Brook, NY, USA; 5The Mays Cancer Center at the University of Texas Health, San Antonio, TX, USA and 6 Medical Service, Northport VA Medical Center, Northport, NY, USA  \n*XY and SL contributed equally as first authors.  \nCorrespondence: H. Zhan  \n[Huichun.Zhan@stonybrookmedicine.edu](Huichun.Zhan@stonybrookmedicine.edu)[ ](Huichun.Zhan@stonybrookmedicine.edu)[Huichun.Zhan@va.gov](Huichun.Zhan@va.gov)  \nReceived: August 13 2025.  \nAccepted: January 12, 2026.  \nEarly view: January 22, 2026.  \n[https://doi.org/10.3324/haematol.2025.288948](https://doi.org/10.3324/haematol.2025.288948)  \n©2026 Ferrata Storti Foundation  \nPublished under a CC BY-NC license   \nAbstract  \nMyeloproliferative neoplasms (MPN) are clonal stem cell disorders characterized by dysregulated megakaryopoiesis and expansion of neoplastic hematopoietic stem cells (HSC) . Megakaryocytes (MK) not only regulate HSC function, but also shape immune responses within the marrow niche. Using an aging murine model of MPN with MK-restricted JAK2V617F expression, we investigated the immunomodulatory roles of mutant MK. Compared to wild-type MK, aged mutant MK exhibit enhanced antigen uptake and MHC I presentation, secretion of pro-inflammatory cytokines (PF4, TGF β, IL-1 β), and induction of T-cell dysregulation in the marrow niche. In chimeric murine models with co-existing wild-type and JAK2V617F mutanthematopoietic cells, enhanced MK immune activity correlates with mutant cell expansion and MPN development. Single-cell RNA sequencing revealed that aging amplifies JAK2V617F MK–driven immune remodeling. Notably, aged mutant MK showed marked upregulation of long-interspersed element-1 (LINE-1) retrotransposon transcripts alongside elevated innate immune sensors cyclic GMP–AMP synthase (cGAS) and stimulator of interferon genes (STING), implicating retrotransposon activity in niche inflammation. In human MPN marrow, immunohistochemistry detected LINE-1–encoded protein ORF1p in MK from 12 of 13 MPN patients, but not in orthopedic controls (N=5) . These findings identify MK as active immune regulators in MPN, with JAK2V617F mutation and aging synergizing to reprogram MK into inflammatory, immune-modulatory niche cells. LINE-1 activation emerges as a potential driver of chronic marrow inflammation, and a targetable mechanism in clonal hematopoiesis and MPN progression.  \nIntroduction  \nMegakaryocytes (MK), traditionally recognized as the precursors of platelets, have emerged as key regulators of hematopoietic stem cell (HSC) function. Through the production of cytokines, chemokines, and extracellular matrix components, MK influence both steady-state and stress hematopoiesis 1-5 Recent studies also suggest that MK contribute to pathogen surveillance and immune regulation.6-11 While abnormal megakaryopoiesis is a common feature of many hematologic malignancies,12-16 how diseased MK alter their immunomodulatory function and impact HSC behavior in normal and neoplastic hematopoiesis remains poorly understood.  \nMyeloproliferative neoplasms (MPN), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are clonal stem cell disor-  \nders characterized by hematopoietic stem/progenitor cell (HSPC) expansion and an increased risk of transformation to acute leukemia. The acquired kinase mutation JAK2V617F plays a central role in these diseases 17,18 MK hyperplasia is a hallmark feature of MPN, with adv","cbCailGtyoOEj5tW","https://ap.wps.com/l/cbCailGtyoOEj5tW","pdf",3213560,"English","# Abstract\n# Introduction\n# Methods","[{\"question\":\"What role do megakaryocytes play in the hematopoietic niche of MPN?\",\"answer\":\"Megakaryocytes regulate hematopoietic stem cell functions and shape immune responses within the marrow niche, influencing both steady-state and stress hematopoiesis.\"},{\"question\":\"How was JAK2V617F-related mutant megakaryocyte immunomodulation studied?\",\"answer\":\"The study used an aging murine MPN model with MK-restricted JAK2V617F expression and compared mutant MK with wild-type MK, including chimeric models and single-cell RNA sequencing.\"},{\"question\":\"What molecular changes connect aging, mutant MK, and marrow inflammation?\",\"answer\":\"Aging amplified JAK2V617F MK-driven immune remodeling and was associated with increased LINE-1 retrotransposon transcripts, elevated cGAS/STING innate immune sensors, and niche inflammation.\"}]","Immunomodulatory role of megakaryocytes in the hematopoietic niche of myeloproliferative neoplasms - Research | PDF",1790141098,35]