Transcriptional signatures (RNA-seq) of AZA pre-treatment CD34+ progenitors isolated from MDS/AML-MRC patients, targeted plasma metabolic profiling and selected immunohistochemistry analyses show that AZA-responders have actively cycling progenitors poised for erythro-myeloid differentiation, with high metabolic activity controlling histone acetylation. Here, CD34 is linked to myelodysplastic syndrome.