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.