Summary: Gene expression is dynamically regulated in a variety of mammalian physiologies. During mammalian aging, there are changes that occur in protein expression that are highly controlled by the regulatory steps in transcription, post‐transcription, and post‐translation. Although there are global profiles of human transcripts during the aging processes available, the mechanism(s) by which transcripts are differentially expressed between young and old cohorts remains unclear. Here, we report on N6‐methyladenosine (m6A) RNA modification profiles of human peripheral blood mononuclear cells (PBMCs) from young and old cohorts. An m6A RNA profile identified a decrease in overall RNA methylation during the aging process as well as the predominant modification on proteincoding mRNAs. The m6A‐modified transcripts tend to be more highly expressed than nonmodified ones. Among the many methylated mRNAs, those of DROSHA and AGO2 were heavily methylated in young PBMCs which coincided with a decreased steady‐state level of AGO2 mRNA in the old PBMC cohort. Similarly, downregulation of AGO2 in proliferating human diploid fibroblasts (HDFs) also correlated with a decrease in AGO2 mRNA modifications and steady‐state levels. In addition, the overexpression of RNA methyltransferases stabilized AGO2 mRNA but not DROSHA and DICER1 mRNA in HDFs. Moreover, the abundance of miRNAs also changed in the young and old PBMCs which are possibly due to a correlation with AGO2 expression as observed in AGO2‐depleted HDFs. Taken together, we uncovered the role of mRNA methylation on the abundance of AGO2 mRNA resulting in the repression of miRNA expression during the process of human aging.

In recent years, the practice of routinely obtaining day 14 bone marrow biopsies during AML intensive induction therapy has been scrutinized. While current guidelines recommend obtaining mid-induction biopsies to gauge early response to treatment and guide potential changes in future management, concerns have been raised that these biopsies may not be as prognostically accurate as hoped and subsequently may result in additional and unwarranted chemotherapy toxicity in select patients. In this review, our goal is to summarize the most recent evidence surrounding day 14 bone marrow biopsies that have been published and clarify the utility of this currently recommended practice. Here, we review major developments in mid-induction biopsy in AML, along with ongoing and future planned studies in this area, outlining the limitations of available data and our future goals.