부산대학교 도서관

Chromosomal rearrangements involving the mixed lineage leukemia (MLL) gene at 11q23 are frequent in adult and childhood acute leukemia and have been associated with an unfavorable prognosis. Recent evidence suggests that MLLgene partners may influence prognosis. Five translocations account for ∼80% of MLLrearrangements: t(4;11)(q21;q23), AFF1/MLL; t(6;11)(q27;q23), MLLT4/MLL; t(9;11)(p22;q23), MLLT3/MLL; t(11;19)(q23;p13.1), MLL/ELL; and t(11;19)(q23;p13.3), MLL/MLLT1. We have designed dual-color, double-fusion fluorescence in situ hybridization (D-FISH) probe sets to identify these translocations. A blinded study was performed for each probe set using 25 normal bone marrow samples, 25 t(4;11), 20 t(6;11), 20 t(9;11), 18 t(11;19p13.1), and 20 t(11;19p13.3) leukemia specimens as defined by chromosome analysis. The findings demonstrated abnormal D-FISH results for 24 of 25 AFF1/MLL, 19 of 20 MLLT4/MLL, all 20 MLLT3/MLL, all 18 MLL/ELL, and all 20 MLL/MLLT1samples, confirming the efficacy of these D-FISH assays in detecting these common MLL/partnertranslocations. Our D-FISH assays were more accurate than chromosome analysis at distinguishing disruption of 19p13.1/ELLfrom that of 19p13.3/MLLT1. We also demonstrated a statistically significant increase in complex/unbalanced MLL/partnertranslocations occurring in pediatric patients versus adult patients (P= 0.02). A normal cutoff of 0.6% was established, suggesting an application for these assays in minimal residual disease detection and disease monitoring.