[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-345054-105":59,"doc-detail-345054-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","dynamic-epigenetic-regulation-of-bclaf1-splicing-in-acute-myeloid-leukemia","Dynamic epigenetic regulation of BCLAF1 splicing in acute myeloid leukemia","","Dysregulated alternative splicing contributes to cancer progression, and BCLAF1 is investigated for its roles in tumorigenesis and drug resistance. In acute myeloid leukemia (AML) cell lines, two unbalanced BCLAF1 isoforms were identified: a full-length oncogenic isoform and a short-length isoform with tumor-suppressive behavior. Epidrug treatment restores the physiological balance of these isoforms. Results indicate a mechanism linking HDAC1 and DNMT3A to BCLAF1 splicing, correlating with healthy versus cancer states of hematopoietic cells.",{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/dynamic-epigenetic-regulation-of-bclaf1-splicing-in-acute-myeloid-leukemia/345054/",{"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/dynamic-epigenetic-regulation-of-bclaf1-splicing-in-acute-myeloid-leukemia/345054.png","ImageObject",300,407,{"name":92,"@type":93},"Ivy","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","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 is the key finding about BCLAF1 isoforms in AML cells?","Question",{"text":112,"@type":113},"Two distinct, unbalanced BCLAF1 isoforms were identified in AML cell lines: a full-length oncogenic isoform and a short-length isoform that appears tumor-suppressive.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do epidrugs affect BCLAF1 splicing?",{"text":117,"@type":113},"Specific epidrugs re-establish the physiological balance between full- and short-length BCLAF1 isoforms, restoring the correct equilibrium.",{"name":119,"@type":110,"acceptedAnswer":120},"Which molecular players are implicated in the regulation of BCLAF1 splicing?",{"text":121,"@type":113},"The regulatory mechanism involves interplay between HDAC1 and DNMT3A, and it correlates with the healthy versus cancerous state of hematopoietic 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},345054,1790190297,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"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":39,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":46},549758252649,"https://ap-avatar.wpscdn.com/avatar/8000253669c5317157?_k=1778319167496531819","[www.nature.com/cddis](www.nature.com/cddis)  \nARTICLE OPEN   \nDynamic epigenetic regulation of BCLAF1 splicing in acute myeloid leukemia  \nGiulia Sgueglia 1, Crescenzo Massaro1,2, Annamaria Muro 1, Ida Lettiero 1, Erika D’Agostino 1, Gregorio Favale1, Nicla Simonelli1, Nunzio Del Gaudio 1,3, Vincenzo Carafa1,4, Tommaso De Marchi 5, Dante Rotili6,7, Sergio Valente 8, Antonello Mai 8, Gianluca Sbardella 9, Mariacarla De Simone 10, Lucia Altucci 1,4,11 ✉ and Carmela Dell’Aversana 1,12,13 ✉  \n© The Author(s) 2026  \n\n|  | Dysregulation of alternative splicing is increasingly associated with cancer development and tumor progression. BCL2-associated transcription factor 1 (BCLAF1) is involved in a wide range of biological processes and it is continuously being investigated due to its intricate function in tumorigenesis and drug resistance. In acute myeloid leukemia (AML) cell lines, we identified two distinct, unbalanced isoforms of BCLAF1: the full-length isoform, which exhibits oncogenic properties, and the short-length isoform, which seems to act as a tumor suppressor. Treatment with specific epidrugs can re-establish the physiological balance of full-and shortlength isoforms, restoring their correct equilibrium. Our results suggest the existence of a newly identified mechanism underlying the regulation of BCLAF1 splicing orchestrated, at least in part, by the interplay between HDAC1 and DNMT3A, and directly correlated with the healthy or cancerous state of hematopoietic cells. Our findings shed light on a novel regulatory axis in AML and |  |\n| --- | --- | --- |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| highlight the potential of epidrugs to restore normal splicing patterns, paving the way for innovative therapies. |  |  |\n|  | Cell Death and Disease (2026)17:344; [https://doi.org/10.1038/s41419-026-08594-4](https://doi.org/10.1038/s41419-026-08594-4) |  |\n|  |  |  |\n\nINTRODUCTION  \nAltered regulation of alternative splicing is a critical event in the generation and development of many types of cancer [1] . Frequently, the alternative splicing mechanism leads to an altered epigenetic chromatin asset, and epigenetic changes can affect the modulation of splicing; conversely, splicing can modulate the expression of various epigenetic factors, highlighting the fact that these two processes are strictly interconnected [2] . One of the major causes of altered splicing is the result of changes in histone epigenetic marks [2] . Such modifications may modify RNA polymerase II processivity and splicing factor recruitment. Oneof the main histone modifications associated with alternative splicing is H3K36me3, enriched only in the exon of actively transcribed genes and probably involved in RNA polymerase II elongation [3, 4] . Also, H3K4me3 modification is linked to alternative splicing, affecting enzyme binding activity of DNA methyltransferases (DNMTs) [2] . DNMT3A is commonly mutated in acute myeloid leukemia (AML) patients (20% of adult cases) and can interact with splicing components, impacting the modulation of global alternative splicin Dysregulation of histone deacetylases (HDACs) plays a crucial role in hematological cancers, as they are often overexpressed in leukemias, particularly in AML with fusion proteins such as AML1-ETO and PML-RARα [5] . The influence of  \nHDACs in the regulation of splicing both physiologically and pathologically is widely reported in literature [3] . Specifically, HDAC1 is involved in the control of alternative splicing [6], although the exact functional role of this enzyme is not yet characterized.  \nBcl-2-associated transcription factor 1 (BCLAF1) is a multifunctional transcriptional factor involved in several biological processes, both in physiological conditions, such as muscle cell proliferation and differentiation [7], and in pathological contexts, including tumor progression and drug/chemotherapy resistance [8, 9] . In physiological conditions, BCLAF1 exerts pro-apoptoti","cbCaiv1ngIkF5h8S","https://ap.wps.com/l/cbCaiv1ngIkF5h8S","pdf",1764863,"English","# Introduction\n## Alternative splicing and cancer\n## Histone marks and splicing crosstalk\n## BCLAF1 functions in physiology and cancer","[{\"question\":\"What is the key finding about BCLAF1 isoforms in AML cells?\",\"answer\":\"Two distinct, unbalanced BCLAF1 isoforms were identified in AML cell lines: a full-length oncogenic isoform and a short-length isoform that appears tumor-suppressive.\"},{\"question\":\"How do epidrugs affect BCLAF1 splicing?\",\"answer\":\"Specific epidrugs re-establish the physiological balance between full- and short-length BCLAF1 isoforms, restoring the correct equilibrium.\"},{\"question\":\"Which molecular players are implicated in the regulation of BCLAF1 splicing?\",\"answer\":\"The regulatory mechanism involves interplay between HDAC1 and DNMT3A, and it correlates with the healthy versus cancerous state of hematopoietic cells.\"}]","Dynamic epigenetic regulation of BCLAF1 splicing in acute myeloid leukemia | PDF",1790056374]