Prevalence And Clinical Significance Of FLT3 Internal Tandem Duplication Mutation In Elderly Acute Myeloid Leukemia

Objective:The mutations of FLT3-ITD(Fms-like tyrosine kinase3,intenal tandem duplication)was one of the most important ones in acute myeloid leukemia,what's more the mutations rate increased with the increase of age.The aim of our study was to detect FLT3-ITD mutations rate in elderly AML patients,to evaluate the role of FLT3-ITD in AML and its clinical significance.Materials and Methods:We used polymerase chain reaction denaturing high performance liquid chromatography(PCR-DHPLC) method to investigate FLT3-ITD mutations rate in 60 cases of de novo AML patients;30 cases were elderly de novo AML patients and others were the non-elderly AML.We set the normal control group of 10 samples from the patients of benign hemopoietic disease.Analysis was performed using the SPSS 11.5 software package.Results:1.FLT3-ITD mutations were found 13 cases among 60 cases(21.67%) by PCR-DHPLC.While there were no mutations identified in ten case-controls.2.The mutations rate of FLT3-ITD was 26.67%(8/30) in elderly AML and was 16.67%(5/30) in non-elderly AML.The difference of FLT3-ITD mutations rate between elderly AML and non-elderly AML had statistic significance3.All mutations of FLT3-ITD were heterozygous.DNA sequence analysis of FLT3-ITD was performed in 4 patients.We found that the mutation located in exon 14; also involved exon 15.The size of duplicated fragment were from 6bp to 100bp and all rearrangement fragment located in reading frame.4.The relationship between FLT3-ITD and FAB types of AML patients:The mutation rates of elderly AML were 25.0%in type M₂(2/8),40.0%in M₃(2/5),25.0%in M₄ (2/8),40.0%in M₅(2/5),0.0%in M₆(0/2),0%in M₀(0/1),0%in M₇(0/0).In non-elderly AML the mutations rate was that M₂ was 16.67%(1/6),M₃ 25.0%(2/8), M₄ 20.0%(1/5),M₅ 14.28%(1/7),M₆ 0.0%(0/0),M₀ 0.0%(0/2),M₇ 0.0%(0/0). We could see that FTL3-ITD mutations were likely to attend in M₃ types,nomatter in elderly or non-elderly AML groups.5.The relationship between FLT3-ITD and karyomite:Karyomite from 24 elderly AML could supply to analyze.The FLT3-ITD were 0.0%(0/2) in t(8;21),25.0%(1/4) in t(15;17),42.9%(6/14) in normal karyotype,0.0%(0/1) in(+8) and 0.0%(0/3) in complex karyotype.Karyomite from 23 no-elderly AML could supply to analyze.The FLT3-ITD were 0.0%(0/3) in t(8;21),16.67%(1/6) in t(15;17),27.3%(3/11) in normal karyotype,0.0%(0/2) in(+8) and 0.0%(0/1) in complex karyotype.There was significantly difference between these groups,we could see that FLT3-ITD positive patients were likely to attend in normal karyotype group.6.The relation between FLT3-ITD mutation and its clinical significance:FLT3-ITD mutations confered a high white cell number,high blast cells in elderly AML.There were no significantly difference in number of platelet and hemoglobin between two groups.7.The therapeutic effect of elderly AML:The complete remission(CR) rate was 37.5% in 8 case FLT3-ITD positive groups and 59.09%in 22 case FLT3-ITD negative groups.The presence of the FTL3-ITD was associated with statistically significant lower CR rate compared with patients not harboring this mutation. 8.We removed M3 leukemia patients because of M3 patients had better prognosis.we analyzed the correlation of the FTL3-ITD mutations rate and its therapeutic effect. FLT3-ITD mutations were found 4 cases among 13 cases of M3 by PCR-DHPLC. The CR rate was 75.0%in 4 case FLT3-ITD positive groups and 87.5%in 9 case FLT3-ITD negative groups.There was no significantly difference between two groups.Conclusions:1.There were no mutations identified in ten case-controls.The rates of FLT3-ITD in elderly AML groups were higher than that of non-elderly AML groups.Our researches indicated that FLT3-ITD mutations positive groups confered a higher white cell number,higher blast cells and lower CR rates.All of which suggested that FLT3-ITD mutations associated with the development of elderly AML.2.we could see that FLT3-ITD positive patients were likely to attend in normal karyotype group.The patients with the mutation had a similar clinical performance and prognosis,which manifested that FLT3-ITD was a molecular potentially useful for the stratification of diagnosis and prognosis of AML,especially for those with normal cytogenetics.A lower complete remission rate suggests that new treatment modalities,sueh as therapy with a FTL3 tyrosine kinase inhibitor,are clearly needed for this group of patients.3.we could see that FLT3-ITD positive patients were likely to attend in M3 group. There was no significantly difference between two groups.