The Effects Of Gut Microbiota Metabolite Trimethylamine-N-oxide(TMAO) Onacute Myeloid Leukemia

Introduction:TMAO is a widely used gut microbiota metabolite in experiments to understand its physiological nature.Currently,various experiments search for its potential role in cancer promotion,prevention and treatment.Objective:The objective of this experiment was to find out whether TMAO as a gut microbiota metabolite can promote the proliferation of THP1 leukemia cells in vitro.Methods:Cultured THP-1 cells were treated with 3 different concentrations of TMAO(0μM,50 μM and 100 μM).Cells were incubated for 24 h,48 h and 72 h.Cell viability were measured by CCK-8 assay a typical test to mark proliferation effects of tested substances.Apoptosis was done to test cell necrosis.Results:In this experiment it was observed that populations of THP1 cells increased,but,overall TMAO significantly did not have effect on the viability of THP-1 cells in a dosedependent manner(P>0.05).The apoptotic assay showed that TMAO could reduce the apoptosis of THP1 cells which might be caused by IDA compared with control groups.Conclusion:The results of this experiment showed that TMAO has no significant effect on increasing proliferation of THP1 cells.Further experiment to understand the relationship between THP-1 promotion effect of TMAO is suggested.The gut microbiota is host-specific,developing throughout an individual’s lifetime.The gut microbiota is susceptible to exogenous and endogenous modifications,and it can be a fundamental driving or contributing factor to many diseases,affecting both local and distant organ systems and having the potential to influence different processes,including hematopoiesis.Furthermore,the gut microbiota can promote host immune maturation locally and systemically,at the molecular,cellular,and organ levels through hematopoiesis.Evidence suggests that gut microbiota impairment may be implicated in hematological diseases;similarly,the levels of certain metabolites generated by gut microbiota are altered in the context of hematological diseases.The nature and characteristics of the cause-andeffect of this relationship remains to be clarified,and thus far,few studies have investigated this relationship,especially the cause-and-effect between the gut microbiota and its metabolites and hematological diseases.Rather,the current evidence related to the gut microbiota and hematological diseases relies merely on association and correlation.It is vital to realize clearly relationship between the gut microbiota and hematological diseases.This review discusses insights into the cause-and-effect gut microbiota and hematological diseases relationship to bring new perspectives and insights into causality through available evidence on gut microbiota association with hematological diseases.A 72-year-old man was referred to the Hematology Department,Qilu Hospital,Shandong University because a persistent fever and lymphocytosis.His white blood cell count was 143.43×109/L,and 56%prolymphocytes.He did not show lymphadenopathy but splenomegaly.Immunophenotyping of prolymphocytes was CD5(+low),CD10(-),CD11c(-),CD19(+),CD20(+),cCD22(+),CD23(-),cCD79a(+),CD79b(+),FMC7(±),CD43(-),CD3(-),CD56(-),CD103(-),HLA-DR(+),and Lambda(+).R-banding and fluorescence in situ hybridization(FISH)revealed that leukemia cells carried extra chromosome 5.Considering the rare occurrence of trisomy 5 found in prolymphocytic leukemia,especially in Asians,we primarily described the patient’s diagnostic and therapeutic information in detail.This study could provide the firsthand materials for precision,medicine and mechanism research in cytogenetics and molecular biology.Clinical Practice Points:The B-cell prolymphocytic leukemia(B-PLL)diagnosis is challenging due to the superposition with mature B-cell leukemia and/or lymphoma.We conducted detailed diagnostic methods and reasonable therapeutic regimens.Then we found cytogenetic aberration of trisomy 5 accompanied with rapid disease progression.We know that median survival of B-PLL is three years after diagnosis,while survival time of this patient was only 1 month.It inferred that trisomy 5 might be a poor prognosis indicator,providing directions for clinical practice in the foreseeable future.