MLL gene rearrangements: Translocations of chromosomal band 11q23 involving the MLL gene, including most AMLs secondary to epipodophyllotoxin, are associated with monocytic differentiation (FAB M4 and M5). The most common translocation, representing approximately 50% of MLL-rearranged cases in the pediatric AML population, is t(9;11)(p22;q23) in which the MLL gene is fused with the MLLT3(AF9) gene. An MLL gene rearrangement occurs in approximately 20% of children with AML.[28,29] However, more than 50 different fusion partners have been identified for the MLL gene in patients with AML. The median age for 11q23/MLL-rearranged cases in the pediatric AML setting is approximately 2 years, and most translocation subgroups have a median age at presentation of younger than 5 years. However, pediatric cases with t(6;11)(q27;q23) and t(11;17)(q23;q21) have significantly older median ages at presentation (12 years and 9 years, respectively).
Outcome for patients with de novo AML and MLL gene rearrangement is generally reported as being similar to that for other patients with AML.[25,28,90,91] However, as the MLL gene can participate in translocations with many different fusion partners, the specific fusion partner appears to influence prognosis, as demonstrated by a large international retrospective study evaluating outcome for 756 children with 11q23- or MLL-rearranged AML. For example, cases with t(1;11)(q21;q23), representing 3% of all 11q23/MLL-rearranged AML, showed a highly favorable outcome with 5-year EFS of 92%. While reports from single clinical trial groups have variably described more favorable prognosis for cases with t(9;11), in which the MLL gene is fused with the AF9 gene, the international retrospective study did not confirm the favorable prognosis of the t(9;11)(p22;q23) subgroup.[25,28,90,92,93,94]
Several 11q23/MLL-rearranged AML subgroups appear to be associated with poor outcome. For example, cases with the t(10;11) translocation are a group at high risk of relapse in bone marrow and the central nervous system (CNS).[25,29,95] Some cases with the t(10;11) translocation have fusion of the MLL gene with the AF10-MLLT10 at 10p12, while others have fusion of MLL with ABI1 at 10p11.2.[96,97] The international retrospective study found that these cases, which present at a median age of approximately 1 year, have a 5-year EFS in the 20% to 30% range. Patients with t(6;11)(q27;q23) and with t(4;11)(q21;q23) also have a poor outcome, with a 5-year EFS of 11% and 29%, respectively, in the international retrospective study. A follow-up study by the international collaborative group demonstrated that additional cytogenetic abnormalities further influenced outcome of children with MLL translocations, with complex karyotypes and trisomy 19 predicting poor outcome and trisomy 8 predicting a more favorable outcome.