{"id":48283,"date":"2025-04-29T05:24:45","date_gmt":"2025-04-29T09:24:45","guid":{"rendered":"https:\/\/www.erdheim-chester.org\/?p=48283"},"modified":"2025-08-23T17:13:09","modified_gmt":"2025-08-23T21:13:09","slug":"tracing-the-origins-of-erdheim-chester-disease","status":"publish","type":"post","link":"https:\/\/www.erdheim-chester.org\/nl\/tracing-the-origins-of-erdheim-chester-disease\/","title":{"rendered":"Tracing the Origins of Erdheim-Chester Disease"},"content":{"rendered":"

The Erdheim-Chester Disease Global Alliance (ECDGA) is honored to support forward-thinking research that helps unravel the mysteries behind Erdheim-Chester Disease (ECD). One of our most compelling funded projects, awarded in 2023 with a two-year, $200,000 research grant, is led by Dr. Matthew Collin in collaboration with Dr. Jyoti Nangalia and Dr. Eli Diamond. Their study,\u00a0\u201cInferring the Origin of Erdheim-Chester Disease from Phylogenetic Mapping,\u201d<\/em>\u00a0is offering new insights into some of the most common and deeply personal questions patients ask: Where did my disease come from? How long have I had it? Could it have been caught earlier?<\/p>\n

This ambitious research project seeks to do more than understand ECD\u2014it aims to trace it back to its earliest moments in a person\u2019s life.<\/p>\n

What Is Phylogenetic Mapping?<\/h3>\n

At the heart of this study is a technique called\u00a0phylogenetic mapping<\/strong>, which is essentially the construction of a \u201cfamily tree\u201d of blood stem cells. The process involves growing single stem cells from a patient\u2019s bone marrow in the lab, sequencing their entire genomes, and then identifying subtle DNA differences between them. These small variations allow researchers to reconstruct the cell\u2019s lineage and timeline, pinpointing when specific mutations\u2014like the ones that cause ECD\u2014occurred.<\/p>\n

This approach gives scientists the ability to\u00a0\u201cdate-stamp\u201d<\/em>\u00a0the ECD-causing mutations and estimate how long those mutations remained dormant before progressing into disease. It also allows them to explore whether additional mutations helped the disease evolve and which biological factors influenced this evolution over time.<\/p>\n

Early Findings: Tracing ECD Over Decades<\/h3>\n

So far, Dr. Collin and Dr Nangalia\u2019s team have studied two patients with high-risk, multisystem ECD\/LCH. Their findings show that in both cases, the mutation responsible for ECD likely originated\u00a0over a decade before symptoms began<\/strong>. Both patients had multiple simultaneous mutations in key genes such as\u00a0KRAS, NRAS, and BRAF<\/strong>, all occurring on separate branches of their phylogenetic trees. Interestingly, all of this unfolded on a background of\u00a0bi-allelic TET2 mutations<\/strong>, which developed much earlier in life.<\/p>\n

These early results suggest that ECD, while rare, may develop over many decades in a way similar to\u00a0myeloproliferative neoplasms<\/strong>, which are far more common blood cancers. This finding not only enhances our understanding of ECD but also bridges its biology with other well-known hematologic conditions.<\/p>\n

Understanding Disease Progression<\/h3>\n

The project aims to answer three core questions:<\/p>\n

    \n
  1. When do ECD-driving mutations occur, and how long do they take to cause disease?<\/strong>
    \n\u2013 Preliminary findings indicate that significant mutations can lie dormant for years or even decades before symptoms arise.<\/li>\n
  2. How do mutations like BRAFV600E interact with earlier genetic changes like TET2?<\/strong>
    \n\u2013 The team found that mutations in the MAPK pathway occurred\u00a0within<\/em>\u00a0TET2-mutated clones, but each operated independently\u2014challenging previous assumptions.<\/li>\n
  3. Are there new, undiscovered mutations that contribute to ECD in patients without known genetic changes?<\/strong>
    \n\u2013 While no new driver mutations have been identified yet, the research is ongoing.<\/li>\n<\/ol>\n

    Overcoming Challenges and Next Steps<\/h3>\n

    One challenge the team faces is studying patients with lower-risk disease. In these individuals, the presence of disease-causing mutations in blood or bone marrow is too sparse to grow usable stem cell clones. However, alternative strategies such as\u00a0primary template amplification<\/strong>\u00a0are being explored, though sequencing errors remain a technical hurdle.<\/p>\n

    In the final phase of the project, Dr. Collin\u2019s team will complete their data analysis, submit abstracts to major scientific meetings (including EHA and the ECDGA symposium), and publish their findings. The goal is to show how ECD emerges through a slow, unique evolutionary process tied to genetic changes that may begin decades before symptoms appear.<\/p>\n

    Waarom dit onderzoek belangrijk is<\/h3>\n

    By tracing the biological history of ECD, this study could open the door to\u00a0earlier detection<\/strong>,\u00a0personalized treatment planning<\/strong>, and even a better understanding of why certain organs are affected in different patients. The insights gained could also help clinicians recognize that although ECD is rare, it shares\u00a0genetic pathways with more common cancers<\/strong>, which may accelerate diagnosis and treatment through broader clinical awareness.<\/p>\n

    At ECDGA, we believe in funding science that transforms lives. This groundbreaking work is only possible through the dedication of researchers like Dr. Collin and the support of our donors and global community.<\/p>\n

    \n

    De Erdheim-Chester Disease Global Alliance (ECDGA) geeft geen medisch advies, stelt geen diagnoses en biedt geen behandelingen aan. Alle inhoud is uitsluitend bedoeld ter informatie. Raadpleeg bij medische vragen een zorgverlener.<\/strong><\/p>","protected":false},"excerpt":{"rendered":"

    The Erdheim-Chester Disease Global Alliance (ECDGA) is honored to support forward-thinking research that helps unravel the mysteries behind Erdheim-Chester Disease (ECD). One of our most compelling funded projects, awarded in […]<\/p>\n","protected":false},"author":20,"featured_media":48284,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_et_pb_use_builder":"","_et_pb_old_content":"","_et_gb_content_width":"","cybocfi_hide_featured_image":"","wds_primary_category":0,"footnotes":"","_links_to":"","_links_to_target":""},"categories":[51],"tags":[],"class_list":["post-48283","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news"],"_links":{"self":[{"href":"https:\/\/www.erdheim-chester.org\/nl\/wp-json\/wp\/v2\/posts\/48283","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.erdheim-chester.org\/nl\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.erdheim-chester.org\/nl\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.erdheim-chester.org\/nl\/wp-json\/wp\/v2\/users\/20"}],"replies":[{"embeddable":true,"href":"https:\/\/www.erdheim-chester.org\/nl\/wp-json\/wp\/v2\/comments?post=48283"}],"version-history":[{"count":0,"href":"https:\/\/www.erdheim-chester.org\/nl\/wp-json\/wp\/v2\/posts\/48283\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.erdheim-chester.org\/nl\/wp-json\/wp\/v2\/media\/48284"}],"wp:attachment":[{"href":"https:\/\/www.erdheim-chester.org\/nl\/wp-json\/wp\/v2\/media?parent=48283"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.erdheim-chester.org\/nl\/wp-json\/wp\/v2\/categories?post=48283"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.erdheim-chester.org\/nl\/wp-json\/wp\/v2\/tags?post=48283"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}