"A novel approach to understanding the role of TCF3 mutations in childhood B-cell precursor acute lymphoblastic leukemia"

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2025-08-13 DOI:10.1016/j.tranon.2025.102505

Monika Lejman , Aleksandra Ozygała , Kinga Wróblewska , Weronika Zegardło , Paulina Widz , Martyna Żyła

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Abstract

The TCF3 (also known as E2A) gene is responsible for encoding a critical transcriptional factor that plays a pivotal role in the differentiation of lymphoid progenitor cells. The TCF3 has been implicated in chromosomal translocations involving various genes, including PBX1, HLF, and ZNF384, as evidenced by recent clinical case studies (rare occuring). These include TLX1, FLI1, and TEF. These rearrangements have been observed to result in uncontrollable proliferation and development of B-cell progenitor acute lymphoblastic leukemia (BCP-ALL). The 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumors distinguishes B-cell lymphoblastic leukemia/lymphoma with TCF3 rearrangement into two types: with TCF3::PBX1 fusion and TCF3::HLF fusion. TCF3-positive pediatric BCP-ALL accounts for 5-11% of patients, making TCF3 an essential component of diagnostic panels for this leukemia. The objective of this manuscript is to provide a comprehensive description of the known TCF3 rearrangements and their associated gene partners. The review will also address the impact of TCF3 fusion genes in pediatric ALL according to the latest data and modern treatments, including the latest research results of Children’s Oncology Group from the 66th American Society of Hematology (ASH) and promising biomarker in B-ALL - circular RNA with regard to TCF3 rearrangements. Additional genetic alterations, termed "secondary hits" are involved in lymphoid development and pathogenesis of ALL. The most frequently observed rearrangements in TCF3 are: PAX5, IKZF1, SETDB2, EBF1, as well as CDKN2A/B.

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一种了解TCF3突变在儿童b细胞前体急性淋巴细胞白血病中的作用的新方法

TCF3（也称为E2A）基因负责编码一个关键的转录因子，该转录因子在淋巴样祖细胞的分化中起关键作用。最近的临床病例研究证实，TCF3与涉及多种基因的染色体易位有关，包括PBX1、HLF和ZNF384（罕见发生）。这些包括TLX1、FLI1和TEF。这些重排已被观察到导致b细胞祖细胞急性淋巴细胞白血病（BCP-ALL）不可控的增殖和发展。世界卫生组织（WHO）第五版《血淋巴样肿瘤分类》将TCF3重排的b细胞淋巴母细胞白血病/淋巴瘤分为两种类型：TCF3::PBX1融合和TCF3::HLF融合。TCF3阳性的儿科BCP-ALL患者占5-11%，使TCF3成为该白血病诊断面板的重要组成部分。本文的目的是提供已知的TCF3重排及其相关基因伙伴的全面描述。本综述还将根据最新数据和现代治疗方法，包括第66届美国血液学会（ASH）儿童肿瘤组的最新研究成果和B-ALL -环状RNA中与TCF3重排有关的有前景的生物标志物，讨论TCF3融合基因对儿童ALL的影响。额外的基因改变，被称为“继发打击”，参与淋巴细胞的发展和ALL的发病机制。TCF3中最常见的重排是：PAX5、IKZF1、SETDB2、EBF1以及CDKN2A/B。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.