Gene expression at a single-molecule level: implications for myelodysplastic syndromes and acute myeloid leukemia

Nongenetic heterogeneity, or gene expression stochasticity, is an important source of variability in biological systems. With the advent and improvement of single molecule resolution technologies, it has been shown that transcription dynamics and resultant transcript number fluctuations generate significant cell-to-cell variability that has important biological effects and may contribute substantially to both tissue homeostasis and disease. In this respect, the pathophysiology of stem cell-derived malignancies such as acute myeloid leukemia and myelodysplastic syndromes, which has historically been studied at the ensemble level, may require reevaluation. To that end, it is our aim in this review to highlight the results of recent single-molecule, biophysical, and systems studies of gene expression dynamics, with the explicit purpose of demonstrating how the insights from these basic science studies may help inform and progress the field of leukemia biology and, ultimately, research into novel therapies.