title: The differential metabolite profiles of acute lymphoblastic leukaemic patients treated with 6-mercaptopurine using untargeted metabolomics approach.
abstract: 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.
authors.affiliation: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA Malaysia, Selangor, Malaysia.
authors.forename: Z
authors.initials: Z
authors.lastname: Bannur
authors.affiliation: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA Malaysia, Selangor, Malaysia; Faculty of Pharmacy, Universiti Teknologi MARA Malaysia, Selangor, Malaysia. Electronic address: tehlaykek@gmail.com.
authors.forename: L K
authors.initials: LK
authors.lastname: Teh
authors.affiliation: Agilent Technologies, 1 Yishun Ave 7, 768923 Singapore.
authors.forename: T
authors.initials: T
authors.lastname: Hennesy
authors.affiliation: Faculty of Pharmacy, Universiti Teknologi MARA Malaysia, Selangor, Malaysia.
authors.forename: W R W
authors.initials: WR
authors.lastname: Rosli
authors.affiliation: Department of Paediatrics, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.
authors.forename: N
authors.initials: N
authors.lastname: Mohamad
authors.affiliation: Department of Paediatrics, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.
authors.forename: A
authors.initials: A
authors.lastname: Nasir
authors.affiliation: Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.
authors.forename: R
authors.initials: R
authors.lastname: Ankathil
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malasia, 43400 UPM Serdang, Selangor, Malaysia.
authors.forename: Z A
authors.initials: ZA
authors.lastname: Zakaria
authors.affiliation: Department of Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.
authors.forename: A
authors.initials: A
authors.lastname: Baba
authors.affiliation: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA Malaysia, Selangor, Malaysia; Faculty of Pharmacy, Universiti Teknologi MARA Malaysia, Selangor, Malaysia. Electronic address: zakisalleh.mzs@gmail.com.
authors.forename: M Z
authors.initials: MZ
authors.lastname: Salleh
mesh_terms: D000293:Adolescent; D000596:Amino Acids / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D015122:Mercaptopurine / Q000627:therapeutic use*; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D009364:Neoplasm Recurrence, Local; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism*; D025341:Principal Component Analysis
chemical_list: D000596:Amino Acids; D015122:Mercaptopurine
keywords: Acute lymphoblastic leukaemia (ALL); Biomarker; Liquid chromatography/mass spectrometry-quadrupole time of flight; Metabolic profiling analysis; Metabolomics