The hypomethylating agent azacitidine (AZA) is used to treat higher-risk myelodysplastic syndromes (HR-MDS) and elderly patients with low-blast count acute myeloid leukemia (LBC-AML). Platelet recovery is an early predictor of AZA response. We prospectively studied the expression profile of transcription factors, critical for late megakaryopoiesis and changes in their expression after AZA treatment in patients with HR-MDS and LBC-AML enrolled in the BMT-AZA trial (EudraCT number 2010-019673-15). Twenty-five additional patients with low-risk (LR)-MDS were also studied. At the time of diagnosis, GATA2 mRNA levels were significantly higher in MDS as compared to controls, with increasing levels from LR- to HR-MDS/AML. RUNX1 expression was also significantly higher in MDS, as compared to controls, but no differences were found between LR- and HR-MDS. Looking at biomarkers of response, we found that patients AZA responsive had higher basal GATA1 and lower FLI1 expression, compared to those with stable or progressive disease after treatment. Univariate analysis showed that increased GATA2 mRNA expression was associated with a worse overall survival. Our findings suggest that high GATA2 expression is a poor prognostic marker for survival in patients with HR-MDS and LBC-AML treated with azacitidine. Moreover, GATA1 and FLI1 mRNA expression may predict response to AZA treatment.
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