47例MLL重排急性白血病患者EVI1和BRE基因表达及其临床意义

OBJECTIVE: To investigate the overexpression frequencies of BRE and EVI1, the correlation between BRE and EVI1 expressions and their possible clinical implications in 11q23/MLL rearrangement acute leukemia. METHODS: Cytogenetic examination of bone marrow cells was performed by short-term culture method. R-banding technique was used for karyotype analysis. 47 patients were detected by interphase fluorescence in situ hybridization (FISH) with dual-color break apart MLL probe. The expressions of EVI1 and BRE genes were detected by real time quantitative reverse transcription polymerase chain reaction (RQ-PCR). The correlation and prognostic significance were statistically tested. RESULTS: 11q23/MLL rearrangements were confirmed by karyotyping and FISH, respectively in 47 patients. According to immunophenotypic analyses of 37 patients, 5 patients showed positive for CD19, CD79a or CD10, 1 for CD7; the others for CD33, CD13, CD14 and CD15, and 16 of them for CD34. Of the 47 patients, 18 patients showed EVI1 overexpression and most of them presented with t(6;11) and M(4)/M(5). The EVI1 expression was high in t(6;11) or t(9;11) subgroup comparable with levels observed in normal subgroup (P=0.038, 0.022, respectively). 15 patients showed high BRE expression, and most of them presented with t(9;11) and M(4)/M(5). High BRE expression was found in t(4;11), t(6;11), t(9;11) and t(11;19) subgroups, respectively by comparing with normal subgroup. The BRE expression was higher in t(4;11) (P=0.004) or t(9;11) (P=0.012) subgroup than in t(6;11) subgroup. Patients with EVI1 overexpression had a short survival compared with those with low EVI1 expression (P=0.049) and it also did in t(9;11) subgroup (P=0.024). Patients with t(9;11) and high BRE expression had a long survival compared with those with t(9;11) and low BRE expression (P=0.024). CONCLUSION: The EVI1 overexpression was significantly frequent in acute leukemia patients with 11q23/MLL rearranged, especially within t(6;11) subgroup and M(4)/M(5), which was associated with an inferior outcome. High BRE expression was observed frequently in 11q23/MLL-rearranged acute leukemia especially within t(9;11) subgroup and M(5).