小儿急性白血病中的梅宁抑制剂:与成人白血病和国际社会合作的全面回顾和加快进展的建议

IF 12.8 1区 医学 Q1 HEMATOLOGY
Branko Cuglievan, Hagop Kantarjian, Jeffrey E. Rubnitz, Todd M. Cooper, C. Michel Zwaan, Jessica A. Pollard, Courtney D. DiNardo, Tapan M. Kadia, Erin Guest, Nicholas J. Short, David McCall, Naval Daver, Cesar Nunez, Fadi G. Haddad, Miriam Garcia, Kapil N. Bhalla, Abhishek Maiti, Samanta Catueno, Warren Fiskus, Bing Z. Carter, Amber Gibson, Michael Roth, Sajad Khazal, Priti Tewari, Hussein A. Abbas, Wallace Bourgeois, Michael Andreeff, Neerav N. Shukla, Danh D. Truong, Jeremy Connors, Joseph A. Ludwig, Janine Stutterheim, Elisabeth Salzer, Kristian L. Juul-Dam, Koji Sasaki, Kris M. Mahadeo, Sarah K. Tasian, Gautam Borthakur, Samantha Dickson, Nitin Jain, Elias Jabbour, Soheil Meshinchi, Guillermo Garcia-Manero, Farhad Ravandi, Eytan M. Stein, E. Anders Kolb, Ghayas C. Issa
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引用次数: 0

摘要

在 KMT2A 重组、NUP98 重组或 NPM1 基因突变的白血病中,HOX 和 MEIS1 家族基因的异常表达会导致分化停滞和白血病的发展。HOX 家族基因是生理性造血的重要看门人,它们的表达受 KMT2A 和 Menin 之间相互作用的调节。Menin 抑制剂可阻断这种相互作用,下调 MEIS1 和其他转录因子的异常表达,从而解除分化阻滞。Menin抑制剂对KMT2A重组和NPM1突变急性白血病有明显的临床疗效,有望满足各种儿童白血病亚型的未满足需求。在这项合作计划中,儿科和成人血液学/肿瘤学专家以及干细胞移植医生联合了他们的专业知识,在国际范围内探索 menin 抑制剂在儿科白血病治疗中的潜力。我们的努力旨在提供有关脑膜素抑制剂的全面临床概述,整合临床前证据和正在进行的全球临床试验的见解。此外,我们还提出了未来国际性、包容性和高效的临床试验设计方案,将儿科人群纳入成人试验中,以确保所有患有脑膜素依赖性白血病的儿童和青少年都能广泛获得这种前景广阔的疗法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Menin inhibitors in pediatric acute leukemia: a comprehensive review and recommendations to accelerate progress in collaboration with adult leukemia and the international community

Menin inhibitors in pediatric acute leukemia: a comprehensive review and recommendations to accelerate progress in collaboration with adult leukemia and the international community

Menin inhibitors in pediatric acute leukemia: a comprehensive review and recommendations to accelerate progress in collaboration with adult leukemia and the international community
Aberrant expression of HOX and MEIS1 family genes, as seen in KMT2A-rearranged, NUP98-rearranged, or NPM1-mutated leukemias leads to arrested differentiation and leukemia development. HOX family genes are essential gatekeepers of physiologic hematopoiesis, and their expression is regulated by the interaction between KMT2A and menin. Menin inhibitors block this interaction, downregulate the abnormal expression of MEIS1 and other transcription factors and thereby release the differentiation block. Menin inhibitors show significant clinical efficacy against KMT2A-rearranged and NPM1-mutated acute leukemias, with promising potential to address unmet needs in various pediatric leukemia subtypes. In this collaborative initiative, pediatric and adult hematologists/oncologists, and stem cell transplant physicians have united their expertise to explore the potential of menin inhibitors in pediatric leukemia treatment internationally. Our efforts aim to provide a comprehensive clinical overview of menin inhibitors, integrating preclinical evidence and insights from ongoing global clinical trials. Additionally, we propose future international, inclusive, and efficient clinical trial designs, integrating pediatric populations in adult trials, to ensure broad access to this promising therapy for all children and adolescents with menin-dependent leukemias.
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来源期刊
Leukemia
Leukemia 医学-血液学
CiteScore
18.10
自引率
3.50%
发文量
270
审稿时长
3-6 weeks
期刊介绍: Title: Leukemia Journal Overview: Publishes high-quality, peer-reviewed research Covers all aspects of research and treatment of leukemia and allied diseases Includes studies of normal hemopoiesis due to comparative relevance Topics of Interest: Oncogenes Growth factors Stem cells Leukemia genomics Cell cycle Signal transduction Molecular targets for therapy And more Content Types: Original research articles Reviews Letters Correspondence Comments elaborating on significant advances and covering topical issues
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