At the present time, we do not have access to predictors of response to hypomethylating agents. MicroRNA (miRNAs) are noncoding RNAs of 19–25 nucleotides in length that regulate gene expression by inducing translational inhibition and cleavage of their target mRNAs through base pairing to partially or fully complementary sites. Altered miRNA expression has been documented in multiples types of leukemia [1]. Acute myeloid leukemia (AML) is a cytogenetically and molecularly heterogeneous disorder characterized by differentiation arrest and malignant proliferation of clonal myeloid precursors. Specific miRNA signatures are associated with cytogenetics and prognosis in AML [2]. Recently it has been reported that pretreatment expression levels of miR-29b are associated with clinical response in patients with AML treated with a 10-day schedule of decitabine [3]. miR-29b is involved in the regulation of DNA methylation and is down regulated in AML [3, 4]. The hypothesis is that patients with higher miR-29b levels would have lower levels of DNA methyltransferase, less hypomethylation, and potentially increased sensitivity to decitabine [3]. This hypothesis is in line with previous observations associating lower levels of p15 methylation with response to decitabine based therapy [5]. The findings of Blum et al.[3] are therefore very significant as detection of miR-29b, if validated, could be used to select hypomethylating-based therapy in AML.

To follow on these observations, we have analyzed miR-29b and miR-101 expression levels in a cohort of patients with AML or high-risk myelodysplastic syndrome treated in a phase I/II study of the combination of 5-azacitidine (5-AZA), valproic acid, and ATRA [6]. We analyzed 45 patients, 28 of which had not received prior therapy. The characteristics of these patients have been previously reported [6]. Eight (29%) patients achieved a complete remission and 1 (4%) partial remission. Total cellular RNA (extracted from unselected peripheral blood mononuclear cells collected before the first cycle of treatment) was used for reverse transcription reactions using Taq-Man miRNA reverse transcription kit (Applied Biosystems). As a control, we also analyzed levels of miR-101. For real-time PCR, miR-29b and miR-101 TaqMan-miRNA assays were purchased from Applied Biosystems and analyzed with TaqMan Universal PCR Master Mix (Applied Biosystems) using an Applied Biosystems Prism 7500 Sequencing detection system. The U6 small nuclear RNA was used