Ectopic expression of a combination of 5 genes detects high risk forms of T-cell acute lymphoblastic leukemia
Li-Jun Peng,
Yue-Bo Zhou,
Mei Geng,
Ekaterina Bourova-Flin,
Florent Chuffart,
Wei-Na Zhang,
Tao Wang,
Meng-Qing Gao,
Meng-Ping Xi,
Zhong-Yi Cheng,
Jiao-Jiao Zhang,
Yuan-Fang Liu,
Bing Chen,
Saadi Khochbin,
Jin Wang,
Sophie Rousseaux,
Jian-Qing Mi
Affiliations
Li-Jun Peng
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
Yue-Bo Zhou
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
Mei Geng
Department of Oncology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Ekaterina Bourova-Flin
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
Florent Chuffart
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
Wei-Na Zhang
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
Tao Wang
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
Meng-Qing Gao
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
Meng-Ping Xi
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
Zhong-Yi Cheng
Jingjie PTM Biolab (Hangzhou) Co., Ldt
Jiao-Jiao Zhang
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
Yuan-Fang Liu
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
Bing Chen
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
Saadi Khochbin
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
Jin Wang
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
Sophie Rousseaux
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
Jian-Qing Mi
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
Abstract 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.