The Role of MicroRNAs in Hematopoietic Stem Cells and Leukemia Development

Hematopoietic stem cells (HSCs) are multipotent cells capable of self-renewal as well as differentiation into all mature blood cell types to sustain lifelong hematopoiesis. Leukemias are thought to be initiated and maintained by leukemic stem cells (LSCs), which also have the capacity for self-renewal, but they are also characterized by varying levels of impaired differentiation and increased proliferation which give rise to disease phenotypes. LSCs and HSCs share the common ability to self-renew, and they may rely on similar pathways for this unique function. Thus, it is critical to understand the molecular mechanisms shared between these two cell populations, as these are likely to represent key features that drive leukemic transformation of HSCs and/or their downstream progeny. Recently, microRNAs (miRNAs) have been implicated as important regulators of self-renewal and differentiation in the hematopoietic system. Profiling of normal and malignant hematopoietic cells, corroborated with a limited but growing number of functional studies, has demonstrated that miRNAs are critical regulators of HSC function, are dysregulated in leukemias, and likely play an important role in leukemogenesis. Herein, we will review these studies and discuss their contributions toward our understanding of the importance of miRNAs in normal and malignant stem cell function in the hematopoietic system.