Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Laboratory of Molecular Pathology, Pôle de Recherches Sino-Français en Science du Vivant Et Génomique, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
BMC Genomics. 2022 Jun 24;23(1):467. doi: 10.1186/s12864-022-08688-1.
T cell acute lymphoblastic leukemia (T-ALL) defines a group of hematological malignancies with heterogeneous aggressiveness and highly variable outcome, making therapeutic decisions a challenging task. We tried to discover new predictive model for T-ALL before treatment by using a specific pipeline designed to discover aberrantly active gene.
The expression of 18 genes was significantly associated with shorter survival, including ACTRT2, GOT1L1, SPATA45, TOPAZ1 and ZPBP (5-GEC), which were used as a basis to design a prognostic classifier for T-ALL patients. The molecular characterization of the 5-GEC positive T-ALL unveiled specific characteristics inherent to the most aggressive T leukemic cells, including a drastic shut-down of genes located on the mitochondrial genome and an upregulation of histone genes, the latter characterizing high risk forms in adult patients. These cases fail to respond to the induction treatment, since 5-GEC either predicted positive minimal residual disease (MRD) or a short-term relapse in MRD negative patients.
Overall, our investigations led to the discovery of a homogenous group of leukemic cells with profound alterations of their biology. It also resulted in an accurate predictive tool that could significantly improve the management of T-ALL patients.
T 细胞急性淋巴细胞白血病（T-ALL）是一组具有异质性侵袭性和高度可变结局的血液系统恶性肿瘤，使得治疗决策成为一项具有挑战性的任务。我们试图通过使用专门设计用于发现异常活跃基因的特定管道，在治疗前发现 T-ALL 的新预测模型。
18 个基因的表达与较短的生存期显著相关，包括 ACTRT2、GOT1L1、SPATA45、TOPAZ1 和 ZPBP（5-GEC），这些基因被用作设计 T-ALL 患者预后分类器的基础。5-GEC 阳性 T-ALL 的分子特征揭示了最具侵袭性 T 白血病细胞固有的特定特征，包括位于线粒体基因组上的基因急剧关闭和组蛋白基因的上调，后者在成年患者中表现为高风险形式。这些病例无法对诱导治疗产生反应，因为 5-GEC 要么预测阳性微小残留病（MRD），要么在 MRD 阴性患者中短期复发。
总体而言，我们的研究导致发现了一组具有深刻生物学改变的同质白血病细胞。它还产生了一种准确的预测工具，可以显著改善 T-ALL 患者的管理。
