Connexin-based signaling in acute myelogenous leukemia (AML)

Normal and malignant hematopoiesis are regulated by intercellular communication in the hematopoietic microenvironments, and both soluble mediators as well as direct cell-cell contact play important functional roles. Gap junctions are complex membrane structures that transfer molecules between neighboring cells and thereby alter intracellular signaling and metabolism. The gap junction building blocks, the connexins, are also involved in gap junction-independent intercellular communication by forming hemichannels that transfer substances between the intra- and extracellular spaces. Connexins are furthermore involved in cell regulation as single molecules by modulating intracellular pathways and possibly gene transcription. The role of connexins in leukemogenesis and leukemic cell functions are not well characterized. In this review, we describe the known effects of gap junctions and connexins in acute myelogenous leukemia and the diverse potential of connexins in acute myelogenous leukemia chemosensitivity, intracellular signaling and cell death regulation. (C) 2009 Elsevier B.V. All rights reserved.