Application of Targeted Therapies and Response Heterogeneity in Two Children With T‐Cell Acute Lymphoblastic Leukemia With BCL11B::TLX3 Fusion Genes

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy that predominantly affects adolescents and young adults, accounting for approximately 15% of all childhood leukemias [ 1, 2 ]. It is characterized by the malignant transformation of T-cell precursors leading to aberrant proliferation. The BCL11B gene plays a pivotal role in T-cell development, and its overexpression or structural variations (such as the BCL11B::TLX3 fusion) can activate the TLX3 oncogene through an enhancer hijacking mechanism, thereby sustaining leukemic cell growth and promoting leukemogenesis [ 3–5 ]. TLX3 is aberrantly expressed in approximately 20% of T-ALL patients, though its precise mechanisms of action remain partially elusive [ 1, 6 ]. Inhibition of BCL11B significantly induces apoptosis and growth arrest in T-ALL cells, highlighting its potential as a therapeutic target [ 3, 7 ]. However, clinical research targeting the BCL11B::TLX3 fusion remains limited, partly due to the rarity of such cases and the complexity of the underlying molecular mechanisms [ 4, 8 ]. This article reports two pediatric cases and aims to explore the application of targeted therapy