Ectopic Expression of a Combination of 5 Genes Detects High Risk Forms of Adult T-cell Acute Lymphoblastic Leukemia
Lijun PengMei GengEkaterina Bourova-FlinFlorent ChuffartWeina ZhangTao WangMengqing GaoMeng-Ping XiZhongyi ChengJiaojiao ZhangYuanfang LiuBing ChenSaadi KhochbinJin WangSophie RousseauxJian‐Qing Mi
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Abstract Objectives 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. Methods A specific pipeline designed to discover aberrantly active genes was applied here on the RNA-sequencing data of 109 T-ALL patients from our multicenter clinical study. A prognostic classifying test, based on the detection of the combined expression of a subset of these genes was designed and further validated in an additional cohort of 32 adult T-ALL patients by using RT-qPCR. 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. 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.Keywords:
Minimal Residual Disease
Ectopic expression
Acute lymphocytic leukemia
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ABSTRACTING & INDEXING
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