Tamibarotene in Higher-Risk Myelodysplastic Syndrome (MDS) - Episode 2

RARA Gene Expression in Higher-Risk MDS

Dr Gustavo Rivero talks about the significance of the RARA gene in patients with higher-risk MDS.

Gustavo Rivero, MD: What does RARA [gene expression] mean in the context of myelodysplastic syndrome [MDS]? I want to emphasize that most of the work has initially been done on acute myelogenous leukemia [AML], and this is an extrapolation of information about such a horrible disease. RARA is normally overexpressed in hematologic malignancy, via activation of super-enhancers. I want to explain what a super-enhancer is. It’s a new form of gene expression in our genome that isn’t expressed in normal conditions. Super-enhancers for RARA have been observed in almost 59% of acute myelogenous leukemia, which I think in the setting of high-risk MDS may be extremely relevant because it might be about the same proportion as in AML. So this overexpression of RARA is counter-regulated by retinoic acid ligands, and there is a significant imbalance between the ligand and the expression of RARA.

We are seeing with significant enthusiasm the development of tamibarotene, which is a RARA agonist that restores the imbalance between the ligand and RARA expression driven by super-enhancers.

Transcript edited for clarity.