Even when tissue-preferential promoters are used to direct transgene expression, off-target and deleterious effects have been observed. The tissue-preferential expression of miRNAs has been exploited to prevent off-target effects in gene therapy studies of mouse models of hemophilia. Unfortunately, the levels of miRNAs Adriamycin identified in primary cells did not correlate well with those detected in the different hematopoietic cell lines. Thus, we cannot extrapolate that miR-125a-5p would be a useful target for restricting transgene expression in primary cells. But for the purpose of testing the hypothesis of exploiting endogenous levels, our data using this miRNA established the potential for developing gene therapy vectors that exploit hematopoietic lineage-preferential miRNA expression. In summary, we have quantified the total RNA and miRNA contents of normal blood hematopoietic cells and identified miRNAs that are DE in a cell-preferential manner. These data can be utilized as a basis for interpretation of miRNA-disease association studies. For example, if a particular miRNA is elevated in acute myelogenous leukemia, but absent or very low in normal granulocytes, this would suggest this miRNA may participate in the pathogenesis of AML. Knowledge of miRNAs DE by blood cell type is also relevant for understanding the systemic effects of blood cell delivered miRNAs. Since all hematopoietic blood cells release microvessicles upon activation, knowledge of these DE miRNAs is expected to be helpful in understanding systemic effects in response to inflammatory and thrombotic stimuli. Lastly, the demonstration that endogenous miRNA levels can be utilized to regulate transgene expression in hematopoietic cell lines suggests an in vitro approach for improving the assessment of gene effects in heterogeneous populations of cultured cells. Considerably more work would be needed to evaluate the value of altering expression vector design for gene therapy of hematological diseases. Furosemide was introduced in the 1960s and is very widely used to treat heart failure and edema. Furosemide and other loop diuretics cause urinary potassium loss, which can lead to potassium depletion and might be expected to increase mortality by mechanisms including ventricular ectopy. On this basis, among others, the 2000 National Council on Potassium in Clinical Practice recommended that potassium supplementation be routinely considered in persons with hypertension receiving a nonpotassium sparing diuretic, and in persons with heart failure even if normokalemic. However, no studies have examined the efficacy or effectiveness of empiric potassium supplementation on reducing the risk of adverse clinical outcomes in users of loop diuretics. As a result of this evidence gap, a 2012 evidence review recommended against the routine use of empiric potassium supplementation in patients receiving loop diuretics, despite the aforementioned practice guidelines. A randomized trial addressing this important question seems unlikely. To provide evidence to help inform this common clinical decision.