3 Sept 2013

Research: Leukaemia cells killed by targeting two kinase enzymes

In recent studies headed by Drs Mark Guthridge and Andrew Wei in the Leukemia Research Group at the ACBD, Monash University, a new and previously unsuspected alliance was identified between the enzymes phosphoinositide 3-kinase (PI3K) and cyclin dependent kinase 9 (Cdk9) in promoting oncogenic survival signals in acute myeloid leukemia (AML) cells.
These studies identified a compound, PIK-75, that simultaneously blocks the activity of both PI3K and Cdk9 and triggers the rapid onset of apoptosis in AML cells but not normal non-malignant bone marrow progenitors. Furthermore, these findings demonstrate that dual targeting of PI3K and Cdk9 with compounds such as PIK-75 has potent anti-leukemic activity against human AML cells both in vitro and in vivo.
Thomas et. al. Targeting acute myeloid leukemia by dual inhibition of PI3K signalling and Cdk9-mediated Mcl-1 transcription. Blood (2013) 122:738-4 http://www.ncbi.nlm.nih.gov/pubmed/23775716

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