The role of reciprocal fusions in MLL-r acute leukemia: studying t(6;11) fusion proteins

We have identified at DCAL two different recombination breakpoints in t(6;11) leukemia patients: those with breakpoints in the major breakpoint cluster region of MLL (introns 9-11; associated with AML), while the other cases displayed breakpoints in the minor breakpoint cluster region (introns 21-23), associated with T-ALL. All 4 fusion genes (MLL-AF6, AF6-MLL, exMLL-AF6, AF6-shMLL) have been cloned, were stably transfected and tested by induced expression (48h) for their molecular functions. Here, we present our DGE results obtained by the „massive amplification of cDNA ends“ technology. Our results indicate that the reciprocal fusion protein AF6-MLL allows to (1) ubiquitously activate chromatin which caused an increased expression of distinct sets of pseudogenes and lncRNAs, and (2) allows a functional synergism with the molecular counterpart MLL-AF6. The exchange of the PHD/BD domain from the der(6) to the der(11) fusion protein in the second set of fusion proteins changed the functional properties of the exMLL-AF6 fusion protein, as a T-cell specific program became activated. This gain-of-function was accompanied by a loss of synergizing with the AF6-shMLL fusion protein.

Publication History

Article published online:
13 May 2020