Clinical Significance And Prognosis Of IAMP21 And ETV6/RUNX1 In Children With Acute B Lymphocytic Leukemia

BackgroundAcute lymphocytic leukemia(ALL)is the most common malignant cancer in childhood,and B-ALL is the most common form of it.With the continuous improvement of treatment methods,most children can achieved remission.There are still some children with recurrence or no remission.As a result,it is very necessary to find out the prognostic factors.By the t(12;21)(p13;q22)translocation leads to ETV6/RUNX1 fusion gene,which is the most common genetic subtype of ALL in children and has a good clinical prognosis.Its clinical significance when combined with other gene copy number variations is unclear.Intrachromosomal amplification of chromosome 21(iAMP21)was detected during routine screening for the presence of the ETV6/RUNX1 fusion by fluorescence in situ hybridization(FISH).Currently,iAMP21 is defined as the presence of multiple RUNX1 signals on chromosome 21.Foreign scholars found that the incidence of iAMP21 was about 2%,and the EFS and OS were significantly lower than those patients with negative iAMP21.However,there is a lack of corresponding research in China.Children with concurrent iAMP21 and ETV6/RUNX1 are extremely rare and have limited clinical data.Only a few cases have been reported abroad.It is of great clinical significance to study the effect of iAMP21 and ETV6/RUNX1 on the prognosis of children with B-ALL.ObjectiveBy analyzing the general clinical characteristics,treatment response and influence on prognosis of children with iAMP21,ETV6/RUNX1,iAMP21 and ETV6/RUNX1,the study wasto determine their clinical effects and prognosis value.MethodsA total of 415 children with acute B-lymphocytic leukemia(B-ALL)admitted to the pediatric ward of the first affiliated hospital of zhengzhou university from January 2013 to December 2015,were selected as subjects.All of them obtained the informed consent of the sick child's family members.4ml of bone marrow fluid was collected before chemotherapy.The expression of iAMP21 and the fusion gene ETV6/RUNX1 were detected using FISH technology.(1)Children were divided into the iAMP21 positive group and the negative group,and the general clinical characteristics,treatment response and influence on prognostic indicators OS,EFS and CRR between the two groups were compared.Multivariate analysis identified prognostic risk factors for B-ALL.(2)The children were divided into ETV6/RUNX1 positive group and negative group,and the clinical characteristics,treatment response and influence on prognosis between the two groups were compared.The proportion of ETV6/RUNX1 in fusion genes was analyzed and compared the prognostic effects with other common fusion genes.The prognosis of the children in the iAMP21 positive group and the ETV6/RUNX1 positive group was further analyzed.(3)To analyze the general characteristics and prognosis of children with coexisting iAMP21 and ETV6/RUNX1.(4)Mortality and recurrence rates were compared between the iAMP21 positive group,ETV6/RUNX1 positive group and the co-existing group.Results1.Among children with B-ALL,the incidence of positive iAMP21 was 2.89%,median age of9.1 years old,with lower WBC and PLT,and the difference was statistically significant compared with the negative group(p<0.05).The CR rate on the 33 th day was lower,and the MRD positive rate on the 33 th day was higher compared with the negative group,the differences were also statistically significant(p<0.05).The EFS and OS at 3 years were 41.6% and 66.7%,respectively,lower than the negative group,and the CRR at 3 years was 58.3%,significantly higher than the negative group,with statistically significant differences(p<0.05).Multivariate analysis confirmedthat positive iAMP21 was an independent indicator of EFS and OS severity.2.In this study,the positive rate of fusion gene was about 17.6%,and the median age was 5.1years old.There was no significant difference in age and gender compared with the negative group(p>0.05).The hepatomegaly rate and the proportion of bone marrow primitive cells were lower than those in the negative group(p<0.05).The therapeutic response on day 8 was significantly worse than that of the negative group(p<0.05).There was no significant difference in MRD on day 31?the CR on day 19,CR on day 33 between the negative group(p>0.05).3.ETV6/RUNX1 has the highest proportion of positive fusion genes among ALL children.By analyzing the EFS at 3 years,ETV6/RUNX1 was significantly higher than other fusion genes(p<0.05).And its EFS at 3 years(77.9%)was slightly higher than that of the negative group,but the difference was not statistically significant(p>0.05).3-year OS(91.9%)was higher than that of the negative group,and 3-year CRR(11.0%)was significantly lower than that of the negative group,with statistically significant differences(p<0.05).4.In our study,3-year EFS was lower in the iAMP21 positive group than in the ETV6/RUNX1 positive group,while 3-year CRR was significantly higher,with statistically significant differences(p<0.05).5.In this study,it was found that children with positive iAMP21 and ETV6/RUNX1 were more rare,with an incidence of only 0.48%.All of them were male and former B-ALL,with older onset age,lower initial white blood cell count.RUNX1 has more than 5 copies.Both cases relapsed in the course of treatment and the prognosis was poor.6.Pairwise comparison between the three groups showed that the mortality and recurrence rates of iAMP21 and ETV6/RUNX1 co-existed groups were higher than those of ETV6/RUNX1 group,and the difference was statistically significant(p<0.0167).The recurrence rate of iAMP21 group was higher than that of ETV6/RUNX1 group,and the difference was also statistically significant(p<0.0167).There was no statistically significant difference in mortality and recurrence rates between the iAMP21 group and the iAMP21 and ETV6/RUNX1 co-existed groups(p>0.0167).Conclusions1.IAMP21 is an independent risk factor for childhood B-ALL.2.ETV6/RUNX1 is the most common fusion gene in children with B-ALL and can be used as a good prognostic indicator.3.The prognosis of B-ALL children with ETV6/RUNX1 and iAMP21 is poor,and the clinical adverse effect of iAMP21 may be greater than the good prognosis effect of ETV6/RUNX1.