[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-330015-105":59,"doc-detail-330015-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","pich-deficiency-limits-the-progression-of-myc-induced-b-cell-lymphoma","PICH deficiency limits the progression of MYC-induced B-cell lymphoma","","Polo-like kinase 1–interacting checkpoint helicase (PICH) is required to resolve anaphase ultrafine DNA bridges and maintain chromosome segregation stability. The study combines new PICH-deficient mouse models with the Eμ-Myc transgenic model to test PICH’s role in Burkitt lymphoma driven by MYC translocations. PICH loss delays lymphoma onset in heterozygous females and improves survival in adult conditional knockouts, with tolerable effects in healthy adults. Findings are validated in human Burkitt lymphoma cell lines where cancer-cell death coincides with chromosomal instability, supporting PICH as a therapeutic target.",{"@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/pich-deficiency-limits-the-progression-of-myc-induced-b-cell-lymphoma/330015/",{"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/pich-deficiency-limits-the-progression-of-myc-induced-b-cell-lymphoma/330015.png","ImageObject",300,407,{"name":92,"@type":93},"Logic","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-14","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is PICH and why is it important in this study?","Question",{"text":112,"@type":113},"PICH (ERCC6L) is a DNA translocase required for resolving anaphase ultrafine DNA bridges, supporting proper chromosome segregation and stability.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does PICH deficiency affect MYC-induced B-cell lymphoma in mice?",{"text":117,"@type":113},"PICH deficiency delays the onset of MYC-induced lymphomas in Pich heterozygous females and adult conditional knockout improves survival of Eμ-Myc transgenic mice.",{"name":119,"@type":110,"acceptedAnswer":120},"Why do the authors propose PICH as a therapeutic target?",{"text":121,"@type":113},"Pich deletion in healthy adult mice is well tolerated, and in human Burkitt lymphoma cell lines, cancer-cell death is accompanied by chromosomal instability, aligning with the therapeutic potential of inhibiting PICH.","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},330015,1790564914,{"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":52,"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,"preview_page_count":4},1099513958762,"https://ap-avatar.wpscdn.com/avatar/1000023916a998db790?x-image-process=image/resize,m_fixed,w_180,h_180&k=1784791008015729253","Blood Cancer [Journal](Journal www.nature.com/bcj)[ www.nature.com/bcj](Journal www.nature.com/bcj)  \nARTICLE OPEN   \nPICH deficiency limits the progression of MYC-induced B-cell lymphoma  \nMaría Castejón-Griñán 1,2, Eliene Albers2, Lucía Simón-Carrasco 1, Paula Aguilera1,2, Mauro Sbroggio2, David Pladevall-Morera2, Andreas Ingham2, Ernest Lim 3, Alba Guillen-Benitez 1, Elena Pietrini 1, Michael Lisby3, Ian D. Hickson2 and  \nAndres J. Lopez-Contreras 1,2 ✉  \n© The Author(s) 2024  \n\n|  | Plk1-interacting checkpoint helicase (PICH) is a DNA translocase involved in resolving ultrafine anaphase DNA bridges and, therefore, is important to safeguard chromosome segregation and stability. PICH is overexpressed in various human cancers, particularly in lymphomas such as Burkitt lymphoma, which is caused by MYC translocations. To investigate the relevance of PICH in cancer development and progression, we have combined novel PICH-deficient mouse models with the Eμ-Myc transgenic mouse model, which recapitulates B-cell lymphoma development. We have observed that PICH deficiency delays the onset of MYC-induced lymphomas in Pich heterozygous females. Moreover, using a Pich conditional knockout mouse model, we have found that Pich deletion in adult mice improves the survival of Eμ-Myc transgenic mice. Notably, we show that Pich deletion in healthy adult mice is well tolerated, supporting PICH as a suitable target for anticancer therapies. Finally, we have corroborated these findings in two human Burkitt lymphoma cell lines and we have found that the death of cancer cells was accompanied by chromosomal instability. Based on these findings, we propose |  |\n| --- | --- | --- |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| PICH as a potential therapeutic target for Burkitt lymphoma and for other cancers where PICH is overexpressed. |  |  |\n|  | Blood Cancer Journal (2024)14:16; [https://doi.org/10.1038/s41408-024-00979-y](https://doi.org/10.1038/s41408-024-00979-y) |  |\n|  |  |  |\n\nINTRODUCTION  \nBurkitt lymphoma (BL) is the most frequent non-Hodgkin’s malignant lymphoma (NHML) to affect children in Europe, and also accounts for 2% of adult NHML [1] . It is an aggressive tumor that arises in various parts of the lymphatic system and is one of the fastest-growing tumors [2] . Although most patients respond well to standard chemotherapy, some patients, especially adults, with relapsed disease have a poor prognosis [3] . Thus, it is still necessary to identify mechanisms and molecular targets that may provide early prognostic markers and/or critical targets for the development of new drugs that block BL initiation and progression. In this regard, targeting pathways involved in the maintenance of chromosomal stability has emerged in the last few years as a promising cancer research area [4] .  \nFaithful chromosomal segregation is critical for the maintenance of genomic stability in every cell division. Polo-like kinase 1 (Plk1)-interacting checkpoint helicase (PICH), encoded by the gene ERCC6L, is required for the resolution of anaphase Ultrafine DNA Bridges (UFBs) and hence for proper chromosome segregation. PICH localizes in the cytosol during interphase but associates with the nuclear DNA after the nuclear envelope breaks down during mitosis [5, 6]. PICH is a DNA translocase with high affinity for DNA under tension [7] and characteristically localizes to UFBs and contributes to their resolution [5, 8]. UFBs are catenated DNA structures derived from unresolved DNA replication intermediates that link the sister chromatids of mitotic chromosomes in anaphase [9, 10] . UFBs can  \narise from different chromosomal loci which are difficult to replicate: telomeres, centromeres, common fragile sites, and ribosomal DNA [9–11] . Failure in the resolution of UFBs at the end of anaphase may lead to chromosomal instability in the daughter cells [8, 12]. UFBs may also play beneficial roles in the maintenance of chromo","cbCaire6PkQDvMkb","https://ap.wps.com/l/cbCaire6PkQDvMkb","pdf",5132880,15,"English","# Introduction\n## Background on Burkitt lymphoma and need for targets\n## Role of PICH and ultrafine DNA bridges in chromosome segregation","[{\"question\":\"What is PICH and why is it important in this study?\",\"answer\":\"PICH (ERCC6L) is a DNA translocase required for resolving anaphase ultrafine DNA bridges, supporting proper chromosome segregation and stability.\"},{\"question\":\"How does PICH deficiency affect MYC-induced B-cell lymphoma in mice?\",\"answer\":\"PICH deficiency delays the onset of MYC-induced lymphomas in Pich heterozygous females and adult conditional knockout improves survival of Eμ-Myc transgenic mice.\"},{\"question\":\"Why do the authors propose PICH as a therapeutic target?\",\"answer\":\"Pich deletion in healthy adult mice is well tolerated, and in human Burkitt lymphoma cell lines, cancer-cell death is accompanied by chromosomal instability, aligning with the therapeutic potential of inhibiting PICH.\"}]","PICH deficiency limits the progression of MYC-induced B-cell lymphoma | PDF",1789986545,38]