| Background and ObjectiveThe core binding factor,also known as polyoma enhancer binging protein 2(PEBP2),refers to a family of heterodimeric transcription factors that play a key role in acute myeloid leukemia,mainly two subtypes of AML1-ETO and CBFβ-MYH11.Since the two nuclear factor-positive AML patients have much similarities and their prognosis is also better than other types of acute myeloid leukemia(except APL),they are classified as core binding factor Acute myeloid leukemia(CBF-AML).However,AML is a heterogeneous group of diseases,even though different leukemias of the same subtype have some differences in the cell biological characteristics and clinical prognosis of leukemia.In the current stratified system,most CBF-AMLs belong to the low-risk group.But when the c-KIT mutations are combined,they are assigned to the middle-risk group.However,some clinically low-risk patients eventually relapse,suggesting that there may be other factors that affect the prognosis of patients with CBF-AML.In addition,although the complete remission rate of CBF-AML as a whole can reach 80% to 90%,the recurrence rate is about 30%,and the 5-year survival rate is only 40% to 60%.Therefore,further study of the clinical features,laboratory characteristics and recurrence risk factors of CBF-AML is still of great significance.Cytogenetics and molecular genetics are closely related to the biological characteristics and prognosis of acute leukemia cells.In recent years,second-generation sequencing has been widely used to evaluate the prognosis of patients with clinical AML,and other molecular genetics associated with CBF-AML have been gradually discovered.Whether it is related to clinical prognosis is not yet clear.This study retrospectively analyzed the general clinical features,treatment outcomes,and prognosis of patients with CBF-AML in our hospital.The aim is to investigate the influence of the clinical features,recurrence risk factors,and changes in cytogenetics and molecular genetics for the prognosis of CBF-AML.Material and methodsThe clinical datas of 1,316 newly diagnosed acute myeloid leukemia(AML)patients aged ≥14 years who were hospitalized in the Department of Hematology of the First Affiliated Hospital of Zhengzhou University between January 2012 and November 2017 were collected.The collected 200 cases of CBF-AML patients were included in the study,including 150 patients with AML1-ETO AML and 50 patients with CBFβ-MYH11 AML.Statistical analysis of general clinical data such as gender and age,laboratory tests,treatment plans and results,follow-up survival time and comparison among groups.Logistic regression was used to analyze the recurrence factors,Kaplan-Meier method was used to draw the survival curve,and log-rank test was used to compare the statistical differences between the survival curves.March 30,2018 was the statistical survival time for the follow-up deadline.Results1.CBF-AML accounted for 15.20%(200/1316)of AML cases,and the ratio of AML1-ETO to CBFβ-MYH11 was 3:1.All patients included 110 males and 90 females,with a median age of 38 years.There were 150 patients in the AML1-ETO group,including 83 males and 67 females,with a median age of 37 years.In the CBFβ-MYH11 group,there were 50 patients,including 27 males and 23 females,with a median age of 39 years.2.In CBF-AML,patients in the CBFβ-MYH11 group had higher leukocyte counts than the AML1-ETO group(47.85×109/L vs 11.30×109/L,P<0.001),and peripheral blood leukemia cells(69.00% vs 42.00%,P<0.001),bone marrow blast cells(76.00% vs 46.40%,P<0.001),β2 microglobulin levels(2.22 mg/L vs 1.67 mg/L,P<0.001),the difference was statistically significant There was no significant difference in gender,age,hemoglobin level,platelet count,lactate dehydrogenase level between the two groups(P>0.05).The CR rate in the CBFβ-MYH11 group was 97.83% and the CR rate in the AML1-ETO group was 87.02%,and the difference between the two groups was statistically significant(P=0.046).While the relapse rate in the CBFβ-MYH11 group was 15.91% and the AML1-ETO group relapsed rate was 29.57%,and the difference between the two groups was not statistically significant(P=0.056).The 2-year overall survival of the AML1-ETO and CBFβ-MYH11 groups were 47.2% 、59.1%,and their difference were not statistically significant(P> 0.05).3.The positive rate of CD56 in AML1-ETO group was 60.0%,and there was no positive patients in CBFβ-MYH11 group,and there was no significantly difference(P<0.001).The positive rate of CD71 in AML1-ETO group was significantly higher than that of CBFβ-MYH11.The positive rate of CD123 in AML1-ETO group was significantly lower than that of CBFβ-MYH11 group(18.00% vs 32.00%,P=0.037).4.The ratio of patients in the low risk cytogenetics group of CBFβ-MH11 group was significantly higher than that of AML1-ETO group(77.55% vs 35.29%,P<0.001);the proportion of patients in the CBFβ-MYH11 group was significantly lower than that of AML1-ETO group(18.37% vs 58.52%,P<0.001);The proportion of high-risk cytogenetics group in CBFβ-MYH11 group had no significant difference compared with AML1-ETO group(4.08% vs 5.93%,P=0.626).Among them,-X,-Y,del(9)abnormalities were found only in the AML1-ETO group,whereas +22 abnormalities were found only in the CBFβ-MYH11 group.At the same time,there was no significant difference in OS between the intermediate-risk cytogenetics group,the high-risk genetics group comparing with the low-risk cytogenetics group(P>0.05).5.In the AML1-ETO group,the CR rate in the low-risk cytogenetics group was 88.37%,the recurrence rate was 38.89%;the CR rate in the moderate-risk cytogenetics group was 86.57%,the recurrence rate was 38.89%;and the high-risk cytogenetic group CR rate was 100%,the recurrence rate was 37.50%;while in the CBFβ-MYH11 group,the low-risk cytogenetics group had a CR rate of 100.00%,a relapse rate of 18.18%,and a CR rate of 100.00% in the genetic group of intermediate-risk nuclear cells,with a recurrence rate of 11.11%.The CR rate of high-risk cytogenetic group was 50.00%,and the recurrence rate was 0.Compared with the low-risk cytogenetics group and the intermediate-risk cytogenetics group,the low-risk cytogenetics group and the high-risk cytogenetics group,respectively,their differences in the cytogenetic alterations for the CR rate or recurrence rate were very small.No statistical significance were found(P >0.05).At the same time,there was no significant difference in OS between the intermediate-risk cytogenetics group,the high-risk genetics group comparing with the low-risk cytogenetics group(P>0.05).6.Of all 200 patients with CBF-AML,93 were detected using one-generation DNA sequencing(65 in the AML1-ETO group and 28 in the CBFβ-MYH11 group).There were 68 mutations detected using the second generation DNA sequencing(52 in AML1-ETO group and 16 in CBFβ-MYH11 group).The detection rate of c-KIT gene mutation was the highest(18.71%).Among them,the detection rate of c-KIT 8 gene mutation in CBFβ-MYH11 group was significantly higher than that in AML1-ETO group(12.20% vs 1.75%,P=0.006).There was no significant difference in the detection rate of c-KIT 17 mutation between the two groups(9.76% vs 16.67%,P=0.286).The detection rates of other gene mutations in patients with CBF-AML were as follows: TET2 mutation 18.06%,NRAS mutation 7.35%,ASXL1 mutation 7.04%,FLT3-ITD mutation 5.63%,CEBPA(single allele)mutation 3.42%,IDH1 The mutation was 2.90%,the U2AF1 mutation was 1.47%,and the FLT3-TKD mutation was 1.04%.There was no significant difference in the detection rates of AML1-ETO and CBFβ-MYH11 between groups(P>0.05).7.68 cases of second-generation gene mutations were grouped according to the risk of molecular genetics.There were 28 low-risk groups,26 moderate-risk groups,and 14 high-risk groups.There was no significant difference in the distribution between the AML1-ETO group and CBFβ-MYH11 group(P >0.05).In patients with AML1-ETO,CR rates were 100%、68.75%and 88.89% in the low-risk,moderate-risk,and high-risk groups,respectively.With the exception that the low-risk group CR rate was significantly higher than the middle-risk group(P=0.008),there was no significant difference in CR rate between the low-risk group and high-risk group(P=0.139),moderate-risk group and high-risk group(P=0.258).The recurrence rates of low-risk group,intermediate-risk group and high-risk group were 15.79% 、27.27 and 0,respectively.There was no significant difference in the recurrence rate between the three groups(P> 0.05).The CR rate in patients with CBFβ-MYH11 was 100%.The recurrence rates of low-risk group,middle-risk group,and high-risk group were 0、14.29% and 50.00%,respectively.There was no significant difference between the three groups(P>0.05).The 2-year OS rates of the low-risk group,the intermediate-risk group,and the high-risk group in the AML1-ETO group were 71.1%,46.2%,and 75.0%,respectively.Compared with the low-risk gene mutation group,the middle-risk gene mutation group and the high-risk gene mutation group,respectively,had no significant difference in OS(P>0.05).And there was no significant difference in OS between the middle-risk group and low-risk group,high-risk group and low-risk group in the CBFβ-MYH11 group(P>0.05).8.68 patients who were tested for second-generation gene mutations were again classified according to the function of the mutated gene and obtained no-gene mutation group,tyrosine kinase signaling pathway-related group,DNA methylationrelated group,transcription factor-related group,and nuclear staining and quality modification related groups were classified.In the AML1-ETO group,the CR rate in the no-gene mutation group was significantly higher than that in the tyrosine kinase signaling pathway-related group(100.00% vs 70.59%,P=0.011)and the DNA methylation-related group(100.00% vs 58.33%,P= 0.002)and nuclear chromatin modification-related groups(100.00% vs 80.00%,P=0.046).There was no significant difference in the recurrence rate among all the groups(P > 0.05).For the comparison of the survival of the above groups of patients,there was no significant difference in OS between each group and the non-gene mutation group(P>0.05).9.Of the 144 patients with KIT mutations,26 had positive c-KIT mutations,the CR rate was 73.08%,the recurrence rate was 15.79%,c-KIT gene mutation was negative in 118 cases,and the CR rate was 93.2%.22.73%.The CR rate of the c-KIT mutation-positive group was significantly lower than that of the negative group(P=0.002),and there was no significant difference in the relapse rate between the two groups(P=0.773).The 2-year RFS of the c-KIT gene mutation-positive group and the negative group was 74.5% and 68.9%,and the 2-year OS was 39.9% and 61.1%.The OS of the c-KIT17 mutation-positive group was significantly lower than that of the c-KIT gene mutation-negative group(P=0.005);between the c-KIT gene mutation-positive group and the negative group,the c-KIT 8 gene mutation-positive group and the negative group,there was no significant difference in OS(P>0.05).10.In 116 patients in the AML1-ETO group,the two-year OS rates in the relapsed group and persistent CR group were 20.90% and 73.10%,respectively,and the difference was statistically significant(P<0.001);the 2-year OS rates of 44 cases in the CBFβ-MYH11 group were 17.10% and 81.20%,respectively,and the difference was statistically significant(P<0.001).CD56 positive was an independent risk factor for CBF-AML recurrence,while age,white blood cell count,bone marrow blast cells,gene mutation risk stratification,cytogenetic risk stratification,and hematopoietic stem cell transplantation did not show significant effects(P>0.05).Of the 175 patients with CBF-AML,71 died during follow-up,cumulative mortality at 2 years was 45.0%,and mortality at 5 years was 53.73%.Risk factors for death were analyzed,among which mortality was significantly higher in patients with low levels of hemoglobin and relapse(P <0.05).Conclusions1 CBF-AML is associated with poor prognosis of c-KIT 17 gene mutation,and other molecular genetic changes and cytogenetic changes have limited effects on treatment and prognosis.2 The positive expression of surface antigen CD56 increases the risk of relapse in patients with CBF-AML.3 Low levels of hemoglobin and recurrence are risk factors for death. |
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