[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-355690-105":59,"doc-detail-355690-en":130},{"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":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","a-specific-stem-cell-program-and-cd112-immunological-axis-dysfunctions-underpinning-monosomy-7-associated-myeloid-neoplasms","A specific stem cell program and CD112 immunological axis dysfunctions underpinning monosomy 7-associated myeloid neoplasms","","Monosomy 7 (−7) occurs in 10–20% of myeloid neoplasms and is linked to poor prognosis, yet its molecular landscape remains incompletely defined. Using an epi-transcriptomic strategy, the study identifies a stemness gene program driven partly by hypermethylated intergenic enhancers and partly by IKZF1/7p12.2 deficiency, leading to CD112 upregulation. In patient-derived CD3+ and NK cells, inhibitory TIGIT and PVRIG increase while activating DNAM1 decreases. Blockade of TIGIT and PVRIG reveals enhanced NK cytolytic activity against −7 leukemic cells, supporting a dysfunctional TIGIT-PVRIG-DNAM1/CD112 axis as a therapeutic avenue.",{"@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/a-specific-stem-cell-program-and-cd112-immunological-axis-dysfunctions-underpinning-monosomy-7-associated-myeloid-neoplasms/355690/",{"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/a-specific-stem-cell-program-and-cd112-immunological-axis-dysfunctions-underpinning-monosomy-7-associated-myeloid-neoplasms/355690.png","ImageObject",300,407,{"name":92,"@type":93},"Rizky","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-26","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},"What problem does the document address about monosomy 7 (−7)?","Question",{"text":112,"@type":113},"It addresses that −7 is common in myeloid neoplasms with poor prognosis, but the −7 molecular landscape is not fully elucidated.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How is CD112 connected to the identified stemness and immunological programs?",{"text":117,"@type":113},"A stemness gene program is linked to hypermethylated enhancers and IKZF1/7p12.2 deficiency, which leads to upregulation of the CD112 immuno-checkpoint gene.",{"name":119,"@type":110,"acceptedAnswer":120},"What therapeutic rationale is tested using the ex vivo TIGIT and PVRIG blockade model?",{"text":121,"@type":113},"The ex vivo model uses cytotoxicity assays showing that blocking TIGIT and PVRIG enhances NK cell cytolytic activity against −7 leukemic 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},355690,1790431431,{"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},962085564807,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","Signal Transduction [and Targeted Therapy](and Targeted Therapy www.nature.com/sigtrans)[ www.nature.com/sigtrans](and Targeted Therapy www.nature.com/sigtrans)  \nA specific stem cell program and CD112 immunological axis dysfunctions underpinning monosomy 7-associated myeloid neoplasms  \nAnair Graciela Lema Fernandez 1, Carlotta Nardelli 1, Martina Quintini 1, Valeria Di Battista 1, Valentina Pierini1, Barbara Crescenzi 1,  \nFabrizia Pellanera 1, Caterina Matteucci 1, Valentina Bardelli 1, Maria Crocioni 1, Giovanni Martino 1, Francesco Maria Adamo 1, Francesca Milano 1, Maria Paola Martelli 1, Pietro Merli 2,3, Loredana Bury 4, Paolo Gorello 1,5, Mattia Forcato 6,  \nFranco Locatelli 2,3, Loredana Ruggeri 1 and Cristina Mecucci 1 ✉  \n|  |  |  |\n| --- | --- | --- |\n|  | Monosomy 7 (−7) is occurring as isolated change or in complex karyotypes in 10–20% of myeloid neoplasms with poor prognosis. Although several genes mapping at chromosome 7 have been involved in pathogenetic mechanisms, the −7 molecular landscape is not fully elucidated. Using an epi-transcriptomic approach, new biological insights emerged in monosomy 7 . A private 49 stemness gene program was first identified and it included 59.2% of the targets of the homeobox transcription factors, specifically deregulated in −7 by hypermethylated intergenic enhancers. Additionally, 20.4% of the stemness program was determined by the signature generated by IKZF1/7p12.2 deficiency, responsible for upregulation of the CD112 immuno-checkpoint gene. Focusing on CD112, immunohistochemistry typically assigned its expression to bone marrow blasts and myeloid progenitors in monosomy 7 . Concomitant increased expression of the inhibitory TIGIT and PVRIG receptors, and decreased expression of the activating DNAM1 receptor, significantly emerged in CD3+, and natural killer (NK) cells from patients with −7 . Moreover, receptors deregulation was shown to be induced by CD34+ leukemic cells with CD112 overexpression. Development of an “ex vivo” model, that used cytotoxicity assays with primary cells from AML cases and autologous NK cells after blockade of the TIGIT and PVRIG receptors, allowed us to show enhanced cytolytic activity of NK against leukemic cells with −7 . Altogether, these results first disclosed a dysfunctional TIGIT-PVRIG-DNAM1/CD112 axis in myeloid neoplasms with monosomy 7, inspiring the use of inhibitory receptors blockade to exploit the NK autologous reactivity against a still undruggable cytogenetic change of myeloid neoplasms with dismal |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| prognosis. |  |  |\n|  | Signal Transduction and Targeted Therapy (2026)11:173 ; [https://doi.org/10.1038/s41392-026-02681-w](https://doi.org/10.1038/s41392-026-02681-w) |  |\n|  |  |  |\n\nINTRODUCTION  \nMyeloid neoplasms (MN) represent a heterogeneous spectrum of hematological disorders arising from the malignant transformation of hematopoietic stem and progenitor cells. This broad category encompasses both Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML), two entities that share biological roots yet markedly differing in clinical presentation and disease course. MDS are characterized by ineffective hematopoiesis resulting from the complex interplay between increased cellular proliferation, enhanced apoptosis, and abnormal differentiation within the bone marrow compartment.1 The typical features are the morphological dysplasia of bone marrow cell lineages, peripheral blood cytopenias, and a heightened propensity to clonal evolution and leukemic transformation.1 Furthermore, the occurrence of MDS features, concomitantly with clinical and laboratory signs of myeloproliferative disorders (MPN), have inspired the diagnostic category of MDS/MPN, included in the  \ninternational classifications.2,3 AML is defined by the clonal expansion of immature myeloid cells, i.e., blasts, in","cbCaivup45bUaPtP","https://ap.wps.com/l/cbCaivup45bUaPtP","pdf",7478321,15,"English","# Introduction\n## Myeloid neoplasms and disease heterogeneity\n## Cytogenetic and molecular drivers\n## Clinical and therapeutic implications","[{\"question\":\"What problem does the document address about monosomy 7 (−7)?\",\"answer\":\"It addresses that −7 is common in myeloid neoplasms with poor prognosis, but the −7 molecular landscape is not fully elucidated.\"},{\"question\":\"How is CD112 connected to the identified stemness and immunological programs?\",\"answer\":\"A stemness gene program is linked to hypermethylated enhancers and IKZF1/7p12.2 deficiency, which leads to upregulation of the CD112 immuno-checkpoint gene.\"},{\"question\":\"What therapeutic rationale is tested using the ex vivo TIGIT and PVRIG blockade model?\",\"answer\":\"The ex vivo model uses cytotoxicity assays showing that blocking TIGIT and PVRIG enhances NK cell cytolytic activity against −7 leukemic cells.\"}]","A specific stem cell program and CD112 immunological axis dysfunctions underpinning monosomy 7-associated myeloid neoplasms | PDF",1790120508,38]