Caspase inhibition blocks apoptosis caused by MLL-AF4 depletion in t(4;11) positive ALL cell lines, but cannot abrogate subsequent necroptosis-like cell death

The reciprocal translocation t(4;11)(q21;q23) is a recurrent chromosomal abnormality in high-risk acute lymphoblastic leukaemia (ALL). This translocation generates the fusion oncogene MLL-AF4. In order to address its functional role in leukaemogenesis, we employ RNA interference (RNAi). We have shown in t(4;11)-positive cell lines that RNAi-mediated depletion of MLL-AF4 induces caspase-dependent apoptosis. In this work we investigated whether inhibition of caspase activity could prevent apoptosis caused by MLL-AF4 knock-down. The t(4;11) positive ALL cell line SEM was transfected with siMLL-AF4, directed against…