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We have investigated MLL rearranged leukemia cases (n = 1590) and present the latest update on this disease entity. About 80 direct MLL fusions and more than 120 reciprocal MLL fusions have been characterized. All patients were classified according to age (infants, pediatric, adult) and their disease phenotype (ALL, AML, others). Of interest, there are significant differences in the MLL breakpoint distribution that allows to draw conclusions about the biology of MLL fusion proteins. Breakpoints in the MLL breakpoint cluster define distinct functions the resulting fusion proteins. Moreover, we will propose a molecular mechanism, by which the most frequent fusion partners disturb normal cell physiology and cause the onset of leukemia.
This work is supported by the grant DKS 2011.09 from the German Children Cancer Aid.