The Expression Of PKM2 In Acute Myeloid Leukmia (Non-M3) And Its Signficane

1? Objective To investigate the expression of Pyruvate kinase(PKM)in acute myeloid leukemia(excluding acute promyelocytic leukemia),we analyze the relationship between expression of Pyruvate kinase(PKM)and pathological data in patients.As well as analyzing the relationship between the expression of PKM2 and the efficacy of AML induction chemotherapy,it provides new ideas for the pathogenesis and clinical diagnosis and treatment of AML.2?Methods Firstly,70 patients with newly diagnosed acute myeloid leukemia(excluding acute promyelocytic leukemia)patients were collected and each patient had at least two courses of coherent treatment.At the same time,35 patients in the normal control group matched by age and sex at the same time were collected.Then,the expression of PKM1 and PKM2 in bone marrow cells of 70 newly diagnosed AML(non-M3)patients and 35 normal controls was detected by real-time PCR(Real-time PCR)technique.PKM2 and karyotype were explored separately.Analysis,clinical pathological parameters of peripheral blood(white blood cell count,hemoglobin count,and platelet count)and bonemarrow blast cell ratio,relationship between five prognostic genes(double CEBPA,NPM1,DNMT3,FLT3-ITD),and efficacy Correlation.3?Results(1)The expression levels of PKM2 and PKM1 in 70 newly diagnosed AML patients and 35 normal controls were measured by Real-time PCR.The results showed that PKM1 and PKM2 were in general compared with the normal control group.The expression level in AML samples was significantly upregulated;the expression of PKM1 was 1.3 times that in the normal control group,P<0.001;the expression level of PKM2 was 1.41 times that of the normal control group,P<0.001;and the ratio of PKM2/PKM1 was the normal control group 1.16 times,P<0.001.The normal karyotype AML and the healthy control group,PKM1 and PKM2 are also significantly upregulated;PKM1 is 1.31 times the normal group,P <0.001,PKM2 is 1.57 times the normal group,P <0.001,PKM2/PKM2 is the normal group 1.23 times,P<0.001.(2)The correlation between the relative expression of PKM2 and the clinical pathological parameters of AML was analyzed,and the results showed that the expression level of PKM2 was negatively correlated with the mutation of doubleCEBPA.(3)Analyzing the relationship between the relative expression of PKM2 and the efficacy of induction chemotherapy,the results showed that PKM2 expression levels were higher in the refractory group than in the CR group and the normal group,P<0.001 and P=0.006,respectively;there was no significant difference between the CR group and the normal group(P=0.989).Univariate analysis of PKM2,clinical features,and laboratory parameters in the AMLpatients in the refractory group and CR group differences between the results showed that: only PKM2 high expression in the AML refractory group and CR group has a statistical difference,P = 0.010.The correlation between PKM2 expression,age,leukocyte count,prognostic gene(double CEBPA,NMP1,FLT3-ITD,DNMT3)and induction chemotherapy response in AML was analyzed using COX regression model.The results showed that PKM2 high expression(P=0.044)is AML Independent adverse factors for the efficacy of induction chemotherapy.4?Conclusion(1)The expression levels of PKM1 and PKM2 in AML patients were significantly higher,and PKM2/PKM1 was significantly higher than normal,suggesting that PKM2 may be involved in the pathogenesis of AML.(2)The high expression of PKM2 was negatively correlated with the mutation rate of double CEBPA.The expression of PKM2 was significantly increased in refractory AML patients and was an independent adverse factor for the efficacy of AML-induced chemotherapy.The association of PKM2 with multiple tumor drug resistance was associated with high expression of PKM2.It may be one of the causes of poor prognosis of AML and may be related to the primary drug resistance of AML chemotherapy.