Study Of Volatile Organic Compounds As New Biomarker For The Diagnosis And Evaluation Of APL

Objective:To study the profiles of the volatile organic compounds(VOCs)from the acute promyelocytic leukemia(APL)cell line NB4 and the breath of APL patients,and to explore the feasibility of the VOC analysis for the diagnosis and therapeutic evaluation of APL.Methods:The VOC profile of the NB4 cells were analyzed by assessing the culture flask headspace gas of the NB4 cells using SPME-GC/MS,as compared to that of the macrophages and the blank medium.With regards to the VOC profiles of APL patients,the breaths of APL patients and healthy volunteers were assessed for the VOC profiles usingSPME-GC/MS.All human subjects were classified into the newly-diagnosed,relapse,remission and healthy groups.The single sample rank sum tests were used to analyze the differences of VOC profiles among each group,in attempt to find novel biological markers for the diagnosis and therapeutic evaluation of the APL.Results:In the headspace gas of the NB4 cells,dimethyl sulfide,o-xylene,1,3-di-tbutyl benzene,acetophenone,dodecane,2,4-dimethylheptane was detected to be significantly higher as compared to those in the control group(p<0.05),with ethanol,benzaldehyde and n-caproaldehyde significantly lower(p< 0.05).Regarding human subjects,dimethylsulfide,methylbenzene and dodecane was significantly higher in the newly-diagnosed group as compared to the healthy control(p< 0.05),with ethanol,benzaldehyde and hexanal lower.Methyl pentenone,methylacetic,n-caprylic alcohol,2-phenyl-2-propanol,ethanol,benzaldehyde and hexanal was higher and dimethylsulfide,methylbenzene and dodecane was lower when the remission group was compared to the newly-diagnosed group.The dimethylsulfide,methylbenzene,dodecane,2-methyl propioric acid,N-dimethylformamide and phenylcarbinol was significantly higher(p< 0.05)and ethanol,benzaldehyde and n-caproaldehyde was lower(p< 0.05)when the relapse group was compared to the remission group.The dimethylsulfide,methylbenzene,dodecane,N-dimethylformamide,phenylcarbinol and 2-methyl propioric acid was significantly higher and ethanol,benzaldehyde and n-caproaldehyde was lower(p< 0.05)when the relapse group was compared to the newly-diagnosed group.Conclusion: Dimethyl sulfide,o-xylene,dodecane,ethanol,benzene,hexanal are VOC candidates as novel biological markers for the diagnosis and therapeutic evaluation of the APL.