Clinical And Laboratory Studies In Acute Leukemia With 11q23/MLL Rearrangements

Objective: To explore the value of fluoresence in situ hybridization (FISH) and reverse transcriptase-multiplex nested polymerase chain reaction(RT-Multiplex Nested PCR) techniques in the detection of mixed lineage leukemia(MLL) rearrangement in AML; To characterize clinical and laboratory features of the acute leukemia with t(6;11)(q27;q23)/MLL gene rearrangement; To report two therapy-related leukemia(TRL) with 1 lq23/MLL rearrngements induced by bimolane or razoxane for their psoriasis. Methods: Dig labeled 11q23 probe which spans the breakpoint cluster region in MLL was used to detect the MLL rearrangement in 23 cases AML including 19 M5 and 4 M4. Setting 3 parallel systems of PCR, common MLL gene rearrangements in 40 AML cases including 12 M4 and 28 M5 were detected by RT-Multiplex Nested PCR technique. The results were compared with conventional cytogenetics(CC). Dual-color MLL probe, whole chromosome paints probes 6 and 11 were used to detect the MLL rearrangements and translocation of 6 and 11 by interphase FISH and chromosome painting in AML cases with t(6;ll)(q27;q23) including 7 M5, 2 M2, 1 acute lymphoblastic leukemia(ALL)-L2. Chromosome painting with whole chromosome painting probes for chromosomes 11 and 19,6 and 11 and D-FISH using Dual-color MLL probe were performed in 2 patients with TRL(1 M4, 1 M5).Results: MLL rearrangements were deteced in 12/23 and 8/40 AML-M4/M5 respectively by FISH and RT-Multiplex Nested PCR. Among 8/40 cases with MLL rearrangements, 6 were chromosome translocation, 2 were MLL partial tandem duplication. All the 10 cases with t(6;l 1) had MLL rearrangements confirmed by Dual-FISH. A reciprocal translocation between 6 and 11 was further confirmed by chromosome painting technique in 5 cases. MLL rearrangement and reciprocal translocation between chromosome 11 and 19 , 6 and11 were also confirmed by D-FISH and chromosome painting respectively. Conclusion: (1) Interphase FISH was more sensitive method for the detection of MLL rearrangement in AML-M4/M5 than convertional cytogenetic (CC) method. (2) MLL rearrangement was hightly associated with AML-M4/M5 and poor prognosis, (g) RT-Multiplex Nested PCR confirmed translocation detected by CC,but also detected MLL partial tandem duplication that could not been detected by CC or FISH. (4) In order to raise the detecting rate of MLL rearrangement, it is necessary to use FISH and/or RT-Multiplex Nested PCR to screen all the patients with acute myelomonocytic/monocytic leukemia. (5) t(6;ll)(q27;q23) acute leukemia had unique clinical features and poor prognosis. (6) chromosome painting technique is a reliable tool for the detection of t(6;ll)(q27;q23). (7)Dioxopiperazine derivatives can induce AML with t(ll;19) and t(6;ll) in adition to inducing AML-M3 with t( 15; 17) , AML-M2 with t(8;21) or t(7; 11). â– END-EN...