The differential metabolite profiles of acute lymphoblastic leukaemic patients treated with 6-mercaptopurine using untargeted metabolomics approach
Background Acute lymphoblastic leukaemia (ALL) has posed challenges to the clinician due to variable patients' responses and late diagnosis. With the advance in metabolomics, early detection and personalised treatment are possible. Methods Metabolomic profile of 21 ALL patients treated with...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
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Elsevier
2014
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| Online Access: | http://psasir.upm.edu.my/id/eprint/35655/ |
| _version_ | 1848848115322322944 |
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| author | Bannur, Zakaria Teh, Lay Kek Hennesy, T. Wan Rosli, Wan Rosalina Mohamad, Norsarwany Nasir, Ariffin Ankathil, Ravindran Zakaria, Zainul Amiruddin Baba, Aziz Salleh, Mohd Zaki |
| author_facet | Bannur, Zakaria Teh, Lay Kek Hennesy, T. Wan Rosli, Wan Rosalina Mohamad, Norsarwany Nasir, Ariffin Ankathil, Ravindran Zakaria, Zainul Amiruddin Baba, Aziz Salleh, Mohd Zaki |
| author_sort | Bannur, Zakaria |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Background
Acute lymphoblastic leukaemia (ALL) has posed challenges to the clinician due to variable patients' responses and late diagnosis. With the advance in metabolomics, early detection and personalised treatment are possible.
Methods
Metabolomic profile of 21 ALL patients treated with 6-mercaptopurine and 10 healthy volunteers were analysed using liquid chromatography/mass spectrometry quadrupole-time of flight (LC/MS Q-TOF). Principal components analysis (PCA), recursive analysis, clustering and pathway analysis were performed using MassHunter Qualitative and Mass Profiler Professional (MPP) software.
Results
Several metabolites were found to be expressed differently in patients treated with 6-mercaptopurine. Interestingly, 13 metabolites were significantly differently expressed [p-value < 0.01 (unpaired t-test) and 2-fold change] in 19% of the patients who had relapses in their treatment. Down-regulated metabolites in relapsed patients were 1-tetrahexanoyl-2-(8-[3]-ladderane-octanyl)-sn-GPEtn, GPEtn (18:1(9Z)/0:0), GPCho(O-6:0/O-6:0), GPCho(O-2:0/O-1:0), methyl 8-[2-(2-formyl-vinyl)-3-hydroxy-5-oxo-cyclopentyl]-octanoate and plasma free amino acids (PFAA). Characterizing the subjects according to their ITPA 94C > A genotypes reveal differential expression of metabolites.
Conclusions
Our research contributes to identification of metabolites that could be used to monitor disease progress of patients and allow targeted therapy for ALL at different stages, especially in preventing complication of relapse. |
| first_indexed | 2025-11-15T09:29:22Z |
| format | Article |
| id | upm-35655 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-15T09:29:22Z |
| publishDate | 2014 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-356552016-01-18T05:15:09Z http://psasir.upm.edu.my/id/eprint/35655/ The differential metabolite profiles of acute lymphoblastic leukaemic patients treated with 6-mercaptopurine using untargeted metabolomics approach Bannur, Zakaria Teh, Lay Kek Hennesy, T. Wan Rosli, Wan Rosalina Mohamad, Norsarwany Nasir, Ariffin Ankathil, Ravindran Zakaria, Zainul Amiruddin Baba, Aziz Salleh, Mohd Zaki Background Acute lymphoblastic leukaemia (ALL) has posed challenges to the clinician due to variable patients' responses and late diagnosis. With the advance in metabolomics, early detection and personalised treatment are possible. Methods Metabolomic profile of 21 ALL patients treated with 6-mercaptopurine and 10 healthy volunteers were analysed using liquid chromatography/mass spectrometry quadrupole-time of flight (LC/MS Q-TOF). Principal components analysis (PCA), recursive analysis, clustering and pathway analysis were performed using MassHunter Qualitative and Mass Profiler Professional (MPP) software. Results Several metabolites were found to be expressed differently in patients treated with 6-mercaptopurine. Interestingly, 13 metabolites were significantly differently expressed [p-value < 0.01 (unpaired t-test) and 2-fold change] in 19% of the patients who had relapses in their treatment. Down-regulated metabolites in relapsed patients were 1-tetrahexanoyl-2-(8-[3]-ladderane-octanyl)-sn-GPEtn, GPEtn (18:1(9Z)/0:0), GPCho(O-6:0/O-6:0), GPCho(O-2:0/O-1:0), methyl 8-[2-(2-formyl-vinyl)-3-hydroxy-5-oxo-cyclopentyl]-octanoate and plasma free amino acids (PFAA). Characterizing the subjects according to their ITPA 94C > A genotypes reveal differential expression of metabolites. Conclusions Our research contributes to identification of metabolites that could be used to monitor disease progress of patients and allow targeted therapy for ALL at different stages, especially in preventing complication of relapse. Elsevier 2014-04 Article PeerReviewed Bannur, Zakaria and Teh, Lay Kek and Hennesy, T. and Wan Rosli, Wan Rosalina and Mohamad, Norsarwany and Nasir, Ariffin and Ankathil, Ravindran and Zakaria, Zainul Amiruddin and Baba, Aziz and Salleh, Mohd Zaki (2014) The differential metabolite profiles of acute lymphoblastic leukaemic patients treated with 6-mercaptopurine using untargeted metabolomics approach. Clinical Biochemistry, 47 (6). pp. 427-431. ISSN 0009-9120; ESSN: 1873-2933 http://www.sciencedirect.com/science/article/pii/S0009912014000745 10.1016/j.clinbiochem.2014.02.013 |
| spellingShingle | Bannur, Zakaria Teh, Lay Kek Hennesy, T. Wan Rosli, Wan Rosalina Mohamad, Norsarwany Nasir, Ariffin Ankathil, Ravindran Zakaria, Zainul Amiruddin Baba, Aziz Salleh, Mohd Zaki The differential metabolite profiles of acute lymphoblastic leukaemic patients treated with 6-mercaptopurine using untargeted metabolomics approach |
| title | The differential metabolite profiles of acute lymphoblastic leukaemic patients treated with 6-mercaptopurine using untargeted metabolomics approach |
| title_full | The differential metabolite profiles of acute lymphoblastic leukaemic patients treated with 6-mercaptopurine using untargeted metabolomics approach |
| title_fullStr | The differential metabolite profiles of acute lymphoblastic leukaemic patients treated with 6-mercaptopurine using untargeted metabolomics approach |
| title_full_unstemmed | The differential metabolite profiles of acute lymphoblastic leukaemic patients treated with 6-mercaptopurine using untargeted metabolomics approach |
| title_short | The differential metabolite profiles of acute lymphoblastic leukaemic patients treated with 6-mercaptopurine using untargeted metabolomics approach |
| title_sort | differential metabolite profiles of acute lymphoblastic leukaemic patients treated with 6-mercaptopurine using untargeted metabolomics approach |
| url | http://psasir.upm.edu.my/id/eprint/35655/ http://psasir.upm.edu.my/id/eprint/35655/ http://psasir.upm.edu.my/id/eprint/35655/ |