Int. J. Environ. Res. Public Health 2012, 9 1940 Keywords: aryl hydrocarbon receptor; gene systems biology expression; leukemia; microRNA; 1. Introduction In the past decade, microRNAs (miRNAs) have emerged as major players in cellular regulation, especially related to carcinogenesis. The expression profiles of miRNAs can be used to classify tumor types and tumor differentiation state with high levels of accuracy [1]. Hematological malignancies, in particular, are considered to be largely influenced by miRNAs. For example, miRNAs are known to regulate hematopoietic stem and/or progenitor cell differentiation [2]. Bone marrow cells from leukemia patients also show significantly altered miRNA expression profiles, where miRNAs related to hematopoiesis are some of the most consistently dysregulated miRNAs in leukemia [3,4]. Because of their role in leukemogenesis, miRNAs are also considered promising therapeutic targets for new leukemia treatment strategies [4]. 1.1. miRNA Background The first miRNA was discovered in Caenorhabditis elegans in 1993 [5]. In 2001 miRNAs received a high level of interest, when they were first reported to act as gene silencers [6,7]. Now seen as important epigenetic regulators, miRNAs play a key regulatory role in mRNA abundance and protein production [8]. By base pairing to target mRNAs, miRNAs can cause mRNA degradation and/or translational repression [9]. Current estimates suggest that mammalian miRNAs regulate more than 60% of all protein-coding genes [10]. Because miRNAs play such pivotal roles in gene regulation, it is important to understand the relationship of miRNAs with disease. 1.2. Acute Myeloid Leukemia (AML) Background Research involving epigenetics has recently focused on the study of cancers with high prevalence and/or mortality rates. For example, leukemia is prevalent in the United States, where it is estimated that 1 in 75 people will be diagnosed during their lifetime [11]. Acute myeloid leukemia (AML) is one of the most common types of leukemia among adults [11]. AML is characterized as a clonal disorder of hematopoietic progenitor cells which have lost the ability to differentiate normally and respond to regulators of proliferation or pro-apoptotic signals [12]. These changes result in the accumulation of progenitor cells arrested at various stages of development, which can eventually lead to fatal infection, bleeding, or organ infiltration [12]. 1.3. Pathways Modulated in Leukemia The mechanisms underlying leukemogenesis often involve changes in cellular signaling, which can inhibit hematopoietic progenitor cells from: (i) responding to normal signals regulating proliferation, and/or (ii) differentiating into mature red blood cells, monocytes, neutrophils, and platelets [12]. Many pathways have been shown to be altered in AML blood and bone marrow cells, including the nuclear