Detection And Clinical Characteristics Of MLL Gene Rearrangement And FLT3/ITD In Acute Leukemia

Objective (1)To study the incidence rate and clinical characteristics of MLL gene rearrangement in AL patients. (2)To approach the incidence rate and clinical characteristics of FLT3/ITD in AL patients.Methods Multiplex nested RT-PCR was used to detect MLL gene rearrangements in 96 cases of acute myeloid leukemia (AML) and 43 cases of acute lymphoblastic leukemia (ALL),with E2A as internal positive control. MLL gene rearrangements include MLL/AF4,MLL/AF6,MLL/AF9,MLL/AF10,MLL/AF17,MLL/ELL,MLL/ENL,MLL/AFX,MLL/AF1P,MLL/AF1Q,MLL-PTD; Immunophenotype was detected by flow cytometry (FCM); PCR was used to detect FLT3/ITD and nucleotide sequencing was used for FLT3/ITD positive cases.Results 10 cases with MLL gene rearrangements were detected in 139 AL patients, 7 cases(7.3%)with MLL gene rearrangements were found in AML patients, including M4 in 3, M5 in 3 and M2 in 1.There were 2 cases of MLL/AF6 fusion gene, 3 cases of MLL/AF9 fusion gene, 1 case of MLL/AF10 fusion gene, and 1 case of MLL-PTD. 3 cases(7.0%)with MLL gene rearrangements were found in ALL patients, they were all B-ALL. There were 2 cases of MLL/AF4 fusion gene, 1 case of MLL/ENL fusion gene. In MLL gene rearrangements group,7 cases with leukocyte count >50×10~9/L,3 cases with leukocyte count≤50×10~9/L,median was 68.45(10.5～154.5)×10~9/L;In MLL gene rearrangements negative group, 36 cases with leukocyte count >50×10~9/L , 93 cases with leukocyte count≤50×10~9/L, median was 24.4(4.5～137.6)×10~9/L,there was statistically significant difference between the two groups(P<0.05). The complete remission (CR) rate of MLL gene rearrangements group was 50%(5/10),that of MLL gene rearrangements negative group was 86.3%(88/129),there was statistically significant difference between the two groups(P<0.05).18 cases (18.8%)with FLT3/ITD were found in 96 AML patients. No case with FLT3/ITD was found in ALL patients.Cases with FLT3/ITD were more found in M3 and present high WBC.Conclusions (1)Multiplex Nested RT-PCR method is a relatively easy and feasible method for detection of MLL gene rearrangements.(2)AML with MLL rearrangement are often detected in M4 and M5, ALL with MLL rearrangement are all B-ALL. (3)Patients with MLL rearrangements present high WBC and dismal prognosis.(4)FLT3/ITD is often detected in AML, cases with FLT3/ITD present high WBC.