Ectopic expression of a combination of 5 genes detects high risk forms of T-cell acute lymphoblastic leukemia
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...
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| Language: | English |
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BMC
2022-06-01
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| Series: | BMC Genomics |
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| Online Access: | https://doi.org/10.1186/s12864-022-08688-1 |
| _version_ | 1811334306186919936 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Li-Jun Peng |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T17:05:52Z |
| format | Article |
| id | doaj.art-39260e69d4ec429bb1b256535fcf0d99 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-04-13T17:05:52Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
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| series | BMC Genomics |
| spelling | doaj.art-39260e69d4ec429bb1b256535fcf0d992022-12-22T02:38:28ZengBMCBMC Genomics1471-21642022-06-0123111410.1186/s12864-022-08688-1Ectopic expression of a combination of 5 genes detects high risk forms of T-cell acute lymphoblastic leukemiaLi-Jun Peng0Yue-Bo Zhou1Mei Geng2Ekaterina Bourova-Flin3Florent Chuffart4Wei-Na Zhang5Tao Wang6Meng-Qing Gao7Meng-Ping Xi8Zhong-Yi Cheng9Jiao-Jiao Zhang10Yuan-Fang Liu11Bing Chen12Saadi Khochbin13Jin Wang14Sophie Rousseaux15Jian-Qing Mi16Shanghai 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 MedicineShanghai 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 MedicineDepartment of Oncology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineLaboratory of Molecular Pathology, Pôle de Recherches Sino-Français en Science du Vivant Et Génomique, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineLaboratory of Molecular Pathology, Pôle de Recherches Sino-Français en Science du Vivant Et Génomique, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 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 MedicineShanghai 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 MedicineShanghai 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 MedicineShanghai 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 MedicineJingjie PTM Biolab (Hangzhou) Co., LdtShanghai 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 MedicineShanghai 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 MedicineShanghai 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 MedicineLaboratory of Molecular Pathology, Pôle de Recherches Sino-Français en Science du Vivant Et Génomique, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 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 MedicineLaboratory of Molecular Pathology, Pôle de Recherches Sino-Français en Science du Vivant Et Génomique, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 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 MedicineAbstract 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.https://doi.org/10.1186/s12864-022-08688-1T-ALLTissue-specific genesPrognosisTranscriptomic profile |
| spellingShingle | 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 Ectopic expression of a combination of 5 genes detects high risk forms of T-cell acute lymphoblastic leukemia BMC Genomics T-ALL Tissue-specific genes Prognosis Transcriptomic profile |
| title | Ectopic expression of a combination of 5 genes detects high risk forms of T-cell acute lymphoblastic leukemia |
| title_full | Ectopic expression of a combination of 5 genes detects high risk forms of T-cell acute lymphoblastic leukemia |
| title_fullStr | Ectopic expression of a combination of 5 genes detects high risk forms of T-cell acute lymphoblastic leukemia |
| title_full_unstemmed | Ectopic expression of a combination of 5 genes detects high risk forms of T-cell acute lymphoblastic leukemia |
| title_short | Ectopic expression of a combination of 5 genes detects high risk forms of T-cell acute lymphoblastic leukemia |
| title_sort | ectopic expression of a combination of 5 genes detects high risk forms of t cell acute lymphoblastic leukemia |
| topic | T-ALL Tissue-specific genes Prognosis Transcriptomic profile |
| url | https://doi.org/10.1186/s12864-022-08688-1 |
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