Epigenetic factors that control acute leukemia cell differentiation

Abstract

Cancer development is a complex process involving diverse tissue types of distinct developmental origins, cell-cell interactions, and a myriad of signaling pathways. Cancer can evolve from a combination of epigenetic and genetic abnormalities resulting in dysregulated gene expression and function. Cells in nearly any part of the body can become cancer. Acute myeloid leukemia (AML) is one of the most common hematologic malignancies and is the more frequent acute leukemia in adults. AML is a complex disease, for which our understanding of the role of genetic and epigenetic changes has undergone significant advancements. Epigenetic changes including histone acetylation and histone methylation play important roles in the onset and progression of AML. Nitric oxide (NO) is a reactive gaseous molecule that influences the physiology and pathophysiology events of organism. NO has been suggested to modulate different cancer-related events. Although not yet clearly stated elsewhere in the literature, NO is an epigenetic molecule. It is known that NO exerts a regulatory function on chromatin and gene expression in cancer. Our previous data showed that THP-1 cells (acute monocytic leukemia cell line) present different profile of histone s-nitrosylation and this event may be related to histones methylation and acetylation, influencing gene transcription. Despite evidence of a detrimental effect of NO-induced protein s-nitrosylation and consequently effect on chromatin and gene expression, the potential participation of s-nitrosylation as epigenetic regulator in acute leukemia cells remain largely understood. Thus, our objective is to evaluate the influence of SNO in different acute leukemia cells and the action of SNO in different epigenetic factors that control acute leukemia cell differentiation. (AU)