Partial duplication of the MLL oncogene in patients with aggressive acute myeloid leukemia

MLL translocations generate a fusion gene between the 5' end of MLL and the 3' end of different partner genes. Several chromosomal mechanisms including complex and cryptic changes lead to these recombinations. Our objective was to analyze the molecular composition of chromosomes in complex karyotypes with specific MLL translocations.

Fluorescence in situ hybridization (FISH) was performed in two acute leukemias (AL), one acute myeloid leukemia (AML) M5a, and one treatment-related-AL (t-AL), to investigate the nature of complex changes accompanying the respective t(9;11)(p22;q23)-MLL/AF9 and t(11;16)(q23;p13.3)-MLL/CBP.

In the case with the MLL/AF9 chimeric transcript, duplication of a der(1) originated from an additional unbalanced translocation between the der(9)t(9;11) and a chromosome 1. The 5'AF9/3'MLL chimeric gene was present on both der(1). In the second case, there was a t(11;16)(q23;p13.3) producing one der(11) and two der(16) which derived from both homologs. One der(16) was present in multiple copies all containing the 5'CBP/3'MLL fusion gene.

In both cases the 3' end of MLL was present in multiple copies. Mitotic recombination and non-disjunction may underlie the extra derivatives in both cases. In this genomic imbalance not only the 5'MLL but also the 3'end of MLL could play a critical role in the leukemic process.