Gigliotti Francesco, Brescia Carolina, Audia Salvatore, Gallo Cantafio Maria Eugenia, Malatesta Paola, Bellisario Michelle-Li, Torcasio Roberta, Cantaffa Renato, Galea Eulalia, Iuliano Rodolfo, Viglietto Giuseppe, Trapasso Francesco, Galati Maria Concetta, Amodio Nicola, Amato Rosario
Renato Dulbecco University Hospital, Catanzaro, Italy.
Dept. of Health Science, Medical School, University "Magna Graecia", Catanzaro, Italy.
Mol Biol Rep. 2025 Sep 18;52(1):922. doi: 10.1007/s11033-025-10979-1.
Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a rare, high-risk subtype of T-ALL characterized by distinctive immunophenotypic and genomic features. It is often associated with induction failure and frequent relapses. Despite recent advances in its molecular characterization, the prognosis remains dismal, and effective targeted therapies are limited.
We report a pediatric, multi-refractory ETP-ALL case with novel cytogenetic alterations, including a 4q deletion and a t(16;18)(q24;q21) translocation. Molecular profiling revealed progressive activation of the BCL2 pathway and disruption of Th17-related immune markers. Ex vivo sensitivity assays performed at different disease stages demonstrated increasing BCL2 dependency. Based on these findings, venetoclax was administered on a compassionate-use basis, resulting in rapid hematologic recovery and a marked reduction in blast percentage.
This case highlights the role of clonal evolution and immune deregulation in accompanying BCL2 addiction in relapsed ETP-ALL. Altogether, our findings underscore the therapeutic potential of venetoclax in refractory pediatric ETP-ALL cases with progressive BCL2 dependency.
早期T细胞前体急性淋巴细胞白血病（ETP-ALL）是T-ALL的一种罕见的高危亚型，其特征为独特的免疫表型和基因组特征。它常与诱导失败和频繁复发相关。尽管最近在其分子特征方面取得了进展，但其预后仍然很差，有效的靶向治疗也很有限。
我们报告了一例患有新型细胞遗传学改变的儿科多难治性ETP-ALL病例，包括4号染色体长臂缺失和t(16;18)(q24;q21)易位。分子谱分析显示BCL2通路的渐进性激活以及Th17相关免疫标志物的破坏。在不同疾病阶段进行的体外敏感性试验表明对BCL2的依赖性增加。基于这些发现，维奈克拉在同情用药的基础上给药，导致血液学快速恢复，原始细胞百分比显著降低。
该病例突出了克隆进化和免疫失调在复发的ETP-ALL中伴随BCL2成瘾的作用。总之，我们的研究结果强调了维奈克拉在具有渐进性BCL2依赖性的难治性儿科ETP-ALL病例中的治疗潜力。
