Hemoglobin F Induction Is Frequent During Low-Dose 5-Aza-2'-Deoxycytidine Treatment Of Older Aml/Mds Patients.

Introduction: DNA hypermethylation is a frequent epigenetic mechanism for gene silencing in various malignancies. Clinical trials of low-dose DNA methyltransferase (DNMT) inhibitors, e.g. 5-aza-2′-deoxycytidine (Dacogen®, DAC) in AML and advanced MDS have shown encouraging activity, and both global and gene-specific in vivo demethylation (e. g. of the p15/INK4b tumor supressor gene) have been reported and valid surrogate markers for effective epigenetic therapy are warranted. DNMT inhibitors were also successfully used to upregulate HbF in patients (pts) suffering from hemoglobinopathies. We wished to investigate whether HbF induction also occurs during AML and MDS treatment with low-dose DAC. Using K562 and HEL myeloid leukemia cell lines which can be induced to erythroid differentiation by hemin and to megakaryocytic differentiation by phorbol myristate acetate (PMA), we also analyzed in vitro changes in globin transcription induced by DAC.