The Clinical Significance Of MLL Rearrangements In Acute Myeloid Leukemia By The Method Of Multiple Nested Reverse Transcription-polymerase Chain Reaction

OBJECTIVE:Leukemia fusion gene detection as leukemia diagnosis, prognosisand minimal residual disease （MRD) detection has been recognized. Mixed lineageleukemia(MLL) gene rearrangements in AML patients always had very poor prognosis.In this study, multiple nested reverse transcription-polymerase chain reaction methodfor the detection of patients with acute myeloid leukemia associatedMLLrearrangements. Reported that the incidence of rearrangements in patients withacute myeloid leukemia MLL gene analysis of clinical significance and prognosticfeatures.METHODS: This study is a retrospective study. From April2008to November2011in the People’s Liberation Army General Hospital.Total433cases of AMLpatients by Multiple nested RT-PCR for screening the eleven MLL gene rearrangementsincidence. Eleven MLL rearrangementsincluded(MLL-PTD,MLL-AF9,MLL-ELL,MLL-AF10,MLL-AF17,MLL-AF6,MLL-ENL,MLL-AF1Q,MLL-CBP,MLL-AF1P,MLL-AFX1) has been screened out.68cases with MLL gene rearrangements, the positive rate of15.7%, We analysis theprognostic features of68MLLrearrangements AML patients.24out of the68patientsunderwent allogeneic hematopoietic stem cell transplantation (Allo-HSCT), and3werelost to follow-up.34of68patients received at least4cycles of chemotherapy;6werelost to follow-up and8had <4cycles of chemotherapy.Two patients underwentAuto-HSCTand eight patients gave up treatment.There were21patients in Allo-HSCTgroup and20patients in the chemotherapy group. We compared two groups OS andDFS.We applied univariate and multivariate methods to analysis prognostic factors.RESULT:24cases of MLL gene rearrangements occur in M5highest number of cases(35.3%). More than11species and gene-positive rate of positive cases were followed by21(4.84%),15(3.46%),10(2.31%),8(1.85%),3(0.69%),3(0.69%),3(0.69%),2(0.46%)1(0.23%)1(0.23%)1(0.23%).MLL gene rearrangements patients, the medianfollow-up time was29months. CR rate of complete remission (35/41) was85.4%,CR1rate (16/41) was39%.The overall recurrence rate (15/41)36.6%.The recurrence ratetransplantation group (6/21) with the chemotherapy alone group (8/20) was (28.6%&40%)restpectively.OS of transplant group and the chemotherapy group were (57.4±5.9&21.0±2.1months, P <0.01). The Allo-HSCT group had superior survival comparedwith the chemotherapy alone group (3-year OS:76±10%vs.32±11%, P<0.01).But inDFS the two groups showed no significant superiority (3years DFS:65±10%vs26±10%, P>0.05).Univariate and multivariate analysis, Treatment options (transplant orchemotherapy)(RR=0.216,95%CI0.125-0.893, P=0.001). Platelet count (>50×109/l or≤50×109/l)(RR=0.221,95%CI:0.073-0.674; P=0.008). CR or not (RR=0.358,95%CI:0.131-0.981; P=0.046) were independent prognostic factors for theOS.Transplantation, platelets>50×109/l and CR have a better prognosis inMLL+AML patients.Extramedullary involvement, WBC>10×109/ldid not affect theOS. Platelet count at onset (>50×109/l or≤50×109/l)(RR=0.154,95%CI:0.033-0.714; P=0.017), and whether extramedullary involvement (RR=4.447,0.95%CI:1.491-13.263; P=0.007) were independent prognostic factors for the DFS.Thrombocytopeniaand extramedullary involvement in MLL+AML patients were proneto relapse. CR transplantation and WBC>10×109/ldid not affect the DFS.After four cycles of chemotherapy or before Allo-HSCTwe detected MRD.Therewere22cases MRD-negative and19caseMRD-positive patients.We compared the twogroups OS and DFS. MRD-negative patients have found a better OS (P=0.001) andDFS (P=0.001)COMCLUSION:Screeningfusion genes by multiplex nested RT-PCR in AMLpatients is convenient, fast, economical and accurate. It is an important method fordiagnosis and prognosis. Our results suggest that Allo-HSCT is superior tochemotherapy alone for treating MLL+AML patients leading to a better prognosis and a longer survival.Platelet count was an independent prognostic factor for OS and DFS.CR is an independent prognostic factor for OS, and extramedullary involvement is anindependent prognostic factor for DFS. MRD-negative patients have better prognosisthanMRD-positive patients.Thrombocytopenia in MLL+AML has very poor prognosis.