儿童 B 细胞急性淋巴细胞白血病中 TCF3 基因重排：单中心经验。

TCF3 gene rearrangements in pediatric B-cell acute lymphoblastic leukemia-A single center experience.

机构信息

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology Oncology and Immunology, Laboratory of Cytogenetics and Molecular Genetics, Moscow, Russian Federation.

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology Oncology and Immunology, Laboratory of Leukemia Immunophenotyping, Moscow, Russian Federation.

出版信息

Int J Lab Hematol. 2023 Aug;45(4):533-540. doi: 10.1111/ijlh.14072. Epub 2023 Apr 14.

DOI:10.1111/ijlh.14072

Abstract

INTRODUCTION

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common neoplasm in children. One of the long known recurrent rearrangements in BCP-ALL is t(1;19)(q23;p13.3)/TCF3::PBX1. However, other TCF3 gene rearrangements were also described that are associated with significant difference in ALL prognosis.

METHODS

The current study aimed to analyze the spectrum of TCF3 gene rearrangements in children in Russian Federation. A cohort of 203 patients with BCP-ALL was selected based on FISH screening and was studied by karyotyping, FISH, RT-PCR and high throughput sequencing.

RESULTS

T(1;19)(q23;p13.3)/TCF3::PBX1 is the most common aberration in TCF3-positive pediatric BCP-ALL (87.7%), with its unbalanced form prevailing. It resulted from TCF3::PBX1 exon 16-exon 3 fusion junction (86.2%) or unconventional exon 16-exon 4 junction (1.5%). Rarer events included t(12;19)(p13;p13.3)/TCF3::ZNF384 (6.4%) and t(17;19)(q21-q22;p13.3)/TCF3::HLF (1.5%). The latter translocations demonstrated high molecular heterogeneity and complex structure-four distinct transcripts were shown for TCF3::ZNF384 and each patient with TCF3::HLF had a unique transcript. These features hamper TCF3 rearrangement primary detection by molecular methods and brings FISH screening to the fore. A case of novel TCF3::TLX1 fusion in a patient with t(10;19)(q24;p13) was also discovered. Survival analysis within the national pediatric ALL treatment protocol demonstrated the severe prognosis of TCF3::HLF compared to both TCF3::PBX1 and TCF3::ZNF384.

CONCLUSION

So, high molecular heterogeneity of TCF3 gene rearrangement in pediatric BCP-ALL was demonstrated and a novel fusion gene TCF3::TLX1 was described.

摘要

简介

B 细胞前体急性淋巴细胞白血病（BCP-ALL）是儿童中最常见的肿瘤。BCP-ALL 中已知的一个长期存在的反复重排是 t(1;19)(q23;p13.3)/TCF3::PBX1。然而，也描述了其他 TCF3 基因重排，这些重排与 ALL 预后有显著差异有关。

方法

本研究旨在分析俄罗斯联邦儿童 TCF3 基因重排的谱。根据 FISH 筛查选择了 203 例 BCP-ALL 患儿的队列，通过核型分析、FISH、RT-PCR 和高通量测序进行研究。

结果

t(1;19)(q23;p13.3)/TCF3::PBX1 是 TCF3 阳性小儿 BCP-ALL 中最常见的异常（87.7%），以不平衡形式为主。它是由 TCF3::PBX1 外显子 16-外显子 3 融合连接（86.2%）或非常规外显子 16-外显子 4 连接（1.5%）引起的。罕见的事件包括 t(12;19)(p13;p13.3)/TCF3::ZNF384（6.4%）和 t(17;19)(q21-q22;p13.3)/TCF3::HLF（1.5%）。后者的易位表现出高度的分子异质性和复杂结构，对于 TCF3::ZNF384 显示了四种不同的转录本，而每个 TCF3::HLF 患者都有一个独特的转录本。这些特征阻碍了 TCF3 重排的主要通过分子方法检测，并使 FISH 筛查成为主要方法。还在 t(10;19)(q24;p13)的患者中发现了一种新的 TCF3::TLX1 融合病例。在国家儿科 ALL 治疗方案的生存分析中，与 TCF3::PBX1 和 TCF3::ZNF384 相比，TCF3::HLF 的预后严重。