15th Congress of the European Hematology Association (EHA), 10 - 13 June, 2010, Barcelona

Interview with Professor Danilo Perrotti  (The Ohio State University, USA)

MicroRNA as a treatment for chronic myelogenous leukaemia

What are you talking about at this meeting?

We are going to talk about the work that was recently published in the March issue of Cell and that is about the discovery of a new function for these small molecules—microRNA.  So microRNAs have the ability to control expression of mRNA by blocking their translations.  So by decreasing the expression of factors regulated by these microRNAs we have found lately that microRNAs can have a different function too.  So they can alter the function of a protein—they enable the protein to act on a particular step of the metabolism.  So this function we call decoy activity.  It’s really a decoy as the mRNA mimics the microRNA and the microRNA binds the protein and blocks the activity of this protein.

So that’s the new function and specifically in myeloid leukaemia what we found is that this microRNA called microRNA - 328 is able to mimic CBP Alpha which is a transcription factor required for myeloid differentiation.  So this transcription factor is lacking in blast crisis CML.  And if you introduce microRNA, you rescue it from differentiation.

What does this microRNA do? In blast crisis when you reconstitute its expression it is able to bind the protein that inhibits the expression of CBP Alpha and therefore rescuing differentiation.  In short if you put back this microRNA into leukemic blast cells the cells are not blasts anymore, they differentiate and then they die.