A Correlation Research Between FLT3-ITD,C-KIT-D816V, NPM1Gene Mutation And Clinical Features, Prognosis In Acute Myeloid Leukemia Patients

Objective:An investigation of mutations of FLT3-ITD、C-KIT-D816V、NPM1has beenconducted among newly diagnosed AML patients to elucidate their correlation withclinical features,efficacy and prognosis.Method：In this study152newly diagnosed AML patients were all from the hematologydepartment of the first affiliated hospital of Nanchang University during March2011to April2013.The mutations of FLT3-ITD and C-KIT-D816V、NPM1(locus A、B、C、D) were examined by PCR and AS-PCR respectively. according to the results, thesepatients were accordingly divided into the following5groups：Group A：FLT3+/NPM1-/C-KIT-，Group B：FLT3-/NPM1+/C-KIT-，Group C：FLT3-/NPM1-/C-KIT+，Group D：FLT3+/NPM1+/C-KIT-，Group E：FLT3-/NPM1-/C-KIT-.First we performed a meticulous investigation and statistical analysis of multiplecharacteristics such as gender, age at first diagnosis, peripheral WBC count,hemoglobin, platelet, ratio of primitive cells in bone marrow, karyotype,etc.Subsequently, compare the incidence rate of each mutation group in FAB subtype.Finally, figure out the CR rate,DFS,OS of each group and compare the differenceamong each group.Results：（1）Among the152AML patients,83cases with normal karyotype and69withabnormal karyotype,the mutation rate of normal karyotype group (46.98%)was higherthan that of abnormal group(40.57%),p>0.05. The mutation rate ofFLT3-ITD,NPM1,C-KIT-D816Vwere18.42%(28/152),30.92%(47/152),3.28%(5/152) respectively andthat of concurrent mutation of FLT3-ITD and NPM1was8.55%（13/152）.（2）FLT3-ITD mutation occured in normal karyotype group was significantlyhigher than that in abnormal karyotype(20.48%vs15.94%,P>0.05).It occured moreoften in M3FAB subtype than others（P<0.05）.Compared with that in the wild gene（mutation-negative）group，statistically significant elevation of peripheral WBCcount and primitive cell ratio were observed （P<0.05）.FLT3-ITD mutationalone(excluded APL)had higher early mortality,lower CR rate,shorter OS withstatistical significance（P<0.05).（3）C-KIT-D816V mutation occured in abnormal karyotype group wassignificantly higher than that in normal karyotype（7.24%vs0%，P<0.05).It occuredmore often in M2FAB subtype than others（P<0.05）.C-KIT-D816V mutation grouphad higher early mortality,shorter OS with statistical significance（P<0.05).（4）FLT3-ITD combine NPM1mutation occured in normal karyotype groupwas higher than that in abnormal karyotype（12.04%vs4.34%，P>0.05).and itoccured more often in M2,M5FAB subtype than others（P＜0.05）.Statisticallysignificant elevation of peripheral WBC count and primitive cell ratio were observed（P<0.05）. FLT3-ITD combine NPM1mutation group had shorter OS thanmutation-negative group(p<0.05).（5）NPM1mutation occured in normal karyotype group was significantlyhigher than that in abnormal karyotype（38.55%vs21.73%，P<0.05).It occured moreoften in M2,M5FAB subtype than others（P<0.05）.The mutation rate of FLT3-ITDwere statistically higher among the NPM1mutation-positive group compared withthat in the control group(27.65%vs14.28%，P<0.05).The NPM1mutation alonegroup had significantly higher CR rate and longer OS（P＜0.05）.Conclusion:（1）Mutations of FLT3-ITD、NPM1、C-KIT-D816V could occur in all AMLpatients.The mutation rate of NPM1was the highest and easily merge FLT3-ITDmutation.（2）FLT3-ITD mutation predominately occured in M3subtype.It showedsignificantly higher peripheral WBC count and primitive cell ratio in the bonemarrow.The following characters were relative to poor prognosis which indicated byhigh early mortality,low CR rate and short OS.（3）C-KIT-D816V mutation mainly occured in abnormal karyotype and M2subtype.The following characters showed poor prognosis as indicated by high earlymortality,low CR rate,short OS. （4）FLT3-ITD combine NPM1mutation mainly occured in M2,M5subtypes.Itshowed significantly higher peripheral WBC count and primitive cell ratio in the bonemarrow.The following characters were relative to poor prognosis which indicated bylow CR rate,short OS.（5）NPM1mutation alone had a preponderant occurrence in normal karyotypeand M2，M5subtypes.The following characters showed good prognosis as indicatedby high CR rate, prolonged OS.