Deepa Sampath, Ph.D. University of Texas MD Anderson Cancer Center

GENETICS

Transcriptional activation to target CLL

Update:

Proteins are produced when genes make messenger RNA (mRNA) that is then translated into proteins. MicroRNAs (miRs) are small molecules that bind to specific mRNA in order to reduce the levels of protein produced by that mRNA. I have identified that specific miRs are not produced in CLL cells. Absence of these miRs causes their target proteins to accumulate. For instance, absence of miRI06b causes its target protein, Itch, to accumulate. Itch causes the destruction of another protein, p73. Reduction in the levels of p73 provides a survival advantage to CLL cells.

I have also identified that the reason these miRs are silenced in CLL is due to the action of a class of proteins, the histone deacetylases, that cause the transcription of these genes to shut off. Chemotherapeutic drugs that inhibit deacetylases cause the re-expression of miRI06b. This causes a reduction in the levels of Itch leading to a reciprocal increase in the levels ofp73. Increases in p73 are linked to activation of proteins that cause cell death in CLL. Thus, these drugs may offer a new therapeutic strategy for the treatment of CLL.