小柯机器人

牛津大学Adam J. Mead团队在研究中取得进展。他们的论文发现了嗜色枯病相关的21号染色体扩增通过DYRK1A的靶向过表达协调转化为爆发期MPN。2025年6月9日出版的《自然—遗传学》发表了这项成果。

在一组64例骨髓增殖性肿瘤（BP-MPN）的母细胞期患者中，课题组研究人员描述了25%的21q染色体区域（'chr.21amp'）的复发性扩增，其中三分之一的患者是由染色体断裂引起的。该研究团队报道。BP-MPN具有特别具有侵袭性和治疗抗性的表型。DYRK1A是一种丝氨酸苏氨酸激酶，是2.7兆碱基最小扩增区中唯一一个与非chr相比表达和染色质可及性都增加的基因。21amp BP-MPN控制。DYRK1A是BP-MPN发育至关重要的多种细胞功能的下一个中心节点，对BP-MPN细胞的体外和体内增殖至关重要，并代表一个可药物轴。总的来说，这些发现定义了chr。21amp作为BP-MPN的预后生物标志物，并将染色体裂解与治疗靶点联系起来。

据介绍，染色体断裂，染色体的混乱破碎和修复，在癌症中很常见。嗜色thripsis是否产生可行的治疗靶点仍然是一个悬而未决的问题。

附：英文原文

Title: Chromothripsis-associated chromosome 21 amplification orchestrates transformation to blast-phase MPN through targetable overexpression of DYRK1A

Author: Brierley, Charlotte K., Yip, Bon Ham, Orlando, Giulia, Wen, Jeremy, Wen, Sean, Goyal, Harsh, Levine, Max, Jakobsdottir, G. Maria, Tapinos, Avraam, Cornish, Alex J., Rodriguez-Romera, Antonio, Rodriguez-Meira, Alba, Bashton, Matthew, Hamblin, Angela, Clark, Sally Ann, Hamley, Joseph C., Fox, Olivia, Giurgiu, Madalina, OSullivan, Jennifer, Murphy, Lauren, Adamo, Assunta, Olijnik, Aude Anais, Cotton, Anitria, Hendrix, Emily, Narina, Shilpa, Pruett-Miller, Shondra M., Enshaei, Amir, Harrison, Claire, Drummond, Mark, Knapper, Steven, Tefferi, Ayalew, Antony-Debr, Ilana, Davies, James, Henssen, Anton G., Thongjuea, Supat, Wedge, David C., Constantinescu, Stefan N., Papaemmanuil, Elli, Psaila, Bethan, Crispino, John D., Mead, Adam J.

Issue&Volume: 2025-06-09

Abstract: Chromothripsis, the chaotic shattering and repair of chromosomes, is common in cancer. Whether chromothripsis generates actionable therapeutic targets remains an open question. In a cohort of 64 patients in blast phase of a myeloproliferative neoplasm (BP-MPN), we describe recurrent amplification of a region of chromosome 21q (‘chr. 21amp’) in 25%, driven by chromothripsis in a third of these cases. We report that chr. 21amp BP-MPN has a particularly aggressive and treatment-resistant phenotype. DYRK1A, a serine threonine kinase, is the only gene in the 2.7-megabase minimally amplified region that showed both increased expression and chromatin accessibility compared with non-chr. 21amp BP-MPN controls. DYRK1A is a central node at the nexus of multiple cellular functions critical for BP-MPN development and is essential for BP-MPN cell proliferation in vitro and in vivo, and represents a druggable axis. Collectively, these findings define chr. 21amp as a prognostic biomarker in BP-MPN, and link chromothripsis to a therapeutic target.

DOI: 10.1038/s41588-025-02190-6

Source: https://www.nature.com/articles/s41588-025-02190-6

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex