Role of peroxisome proliferator-activated receptor-γ in hematologic malignancies

Abstract

Members of the nuclear receptor superfamily, including retinoic acid receptors (RARs), retinoid X receptors (RXRs), and vitamin D receptors (VDRs), are transcription factors that control many important cellular functions, and their ligands are widely used in several clinical indications. The latest family member is the peroxisome proliferator-activated receptor-γ (PPARγ), which is highly expressed in normal monocytes, different leukemias, and epithelial malignancies. PPARγ ligands have been developed and signal differentiation, growth arrest, and apoptosis. PPARγ forms heterodimers with RXR, and ligation of both receptors is required for maximal signaling. PPARγ signaling, its expression in hematologic malignancies, and role in differentiation are discussed. Interactions of PPARγ with X-RARα, protein kinase R (PKR), PTEN, and mitogen-activated protein kinase (MAPK) have been described. PPARγ ligands have been developed for the management of diabetes, but new and more potent ligands, including triterpenoids, are being investigated as therapeutic agents for epithelial and hematologic malignancies.