The Expression And Significance Of BATF, CST1, PLD1 And PTHLH Gene In The Patients Of Chronic Myelogenous Leukemia

Objective:Chronic myelogenous leukemia(CML)is a myeloproliferative disorders caused by malignant proliferation of the multi-functional hematopoietic stem cells.Studies have shown that the presence of the vast majority of patient-specific Ph chromosome is the result of 9 and 22 chromosome translocation.Abl proto-oncogene translocation chromosome 9(9q34)and chromosome 22 on bcr gene(22q11)on re-combined to form fusion genes,BCR-ABL fusion gene,which encodes a protein having tyrosine kinase activity.BCR-ABL fusion gene can activate multiple signaling pathways(including RAS,MAPK,PI-3K / Akt / mTOR,STAT5,etc.),in order to achieve the purpose of promoting the transformation and proliferation of hematopoietic cells.Currently tyrosine kinase inhibitors(TKIs)therapy has been widely used in clinical.TKIs can significantly reduced mortality and improved 5 year survival rates.But with the widely use of TKI in clinical,TKI resistance situation also appeared.Therefore,we may need to look for other targets or other drugs to treat CML.Our study on the Gene Expression Profile of Chronic Myelogenous Leukemia Bone Marrow Mesenchymal Stem Cells(BMMSCs)showed that CML blast crisis and chronic phase BMMSCs certainly exist differences on gene expression.The four genes have remarkable differences between CML blast phase and chronic phase,the expression levels of BATF gene of blastic phase was significant lower than chronic phase,and the expression levels of CST1,PLD1 and PTHLH gene of blastic phase was significant higher than chronic phase.So we detection the expression levels of these four gene in CML patients bone marrow mononuclear cells(BMMNCs),and compare the expression trends of these genes between BMMSCs and BMMNCs.The purpose of this research is to study the expression level of BATF,CST1,PLD1 and PTHLH gene in the bone marrow mononuclear cells of CML patients,then finding new targets for CML therapy.Compare the expression trends of these genes between BMMSCs and BMMNCs,and explore the relationship between the abnormal expression of genes in BMMSCs and the pathogenesis of chronic myelogenous leukemia.Methods:1 Collect of bone marrow specimens chronic myelogenous leukemia chronic phase and blastic phase patients(specimens from the Second Hospital of Hebei Medical University,Department of Hematology),a total of 35 cases,the first experimental group for CML-CP group,a total of 25 cases;the second experimental group CML-BP group,a total of 10 cases.Another 10 cases of Non-hematological malignancies patients as a control group.All bone marrow fluid samples using lymphocytes isolated mononuclear cells were extracted and stored at-80?.2 Using RT-PCR method to detect the expression levels of BATF,CST1,PLD1 and PTHLH gene at the mRNA level.3 Using the Western Blot method to detect the expression of these four genes at the protein level.4 Analysis data by Statistics.Results:1 Clinical specimens used in this experiment showed BATF,CST1,PLD1 and PTHLH gene were expressed at mRNA and protein level.2 Expression of BATF,CST1,PLD1 and PTHLH gene at mRNA level: RT-PCR results showed that the expression levels of BATF,CST1,PLD1 and PTHLH gene at mRNA level in the patients of chronic phase and blastic phase of chronic myeloid leukemia were higher than normal control group(P <0.05),and the expression levels of these four genes in blastic phase was higher than in chronic phase(P <0.05).3 Expression of BATF,CST1,PLD1 and PTHLH gene at protein level: RT-PCR results showed that the expression levels of BATF,CST1,PLD1 and PTHLH gene at protein level in the patients of chronic phase and blastic phase of chronic myeloid leukemia were higher than normal control group(P <0.05),and the expression levels of these four genes in blastic phase was higher than in chronic phase(P <0.05).Conclusion:1 With the progression of chronic myelogenous leukemia,expression levels of BATF,CST1,PLD1 and PTHLH genes mRNA showed a increasing trend.2 With the progression of chronic myelogenous leukemia,expression levels of BATF,CST1,PLD1 and PTHLH genes protein showed a increasing trend.3 BATF,CST1,PLD1 and PTHLH genes may play important roles in the progression of chronic myeloid leukemia.4 Expression of CST1,PLD1,CST1 gene in BMMNCs and BMMSCs have a same trend,but the trend of BATF expression in BMMNCs is different from BMMSCs.