Ectopic expression of a combination of 5 genes detects high risk forms of T-cell acute lymphoblastic leukemia

作者：Lijun Peng, Yue-Bo Zhou, Mei Geng, Ekaterina Bourova-Flin, Florent Chuffart, Weina Zhang, Tao Wang, Mengqing Gao, Meng-Ping Xi, Zhongyi Cheng, Jiaojiao Zhang, Yuanfang Liu, Bing Chen, Saadi Khochbin, Jin Wang, Sophie Rousseaux, Jian‐Qing Mi · 发表于：BMC Genomics · 年份：2022 · DOI：10.1186/s12864-022-08688-1 · 被引用次数：9 · 研究领域：Acute Lymphoblastic Leukemia research、Acute Myeloid Leukemia Research、Lymphoma Diagnosis and Treatment

BACKGROUND: 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. RESULTS: 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. CONCLUSION: 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.