title: Hematopoiesis and retinoids: development and disease.
abstract: Retinoids function as activating ligands for a class of nuclear receptors that control gene expression programs for a wide range of tissues and organs during embryogenesis and throughout life. Over the years, three sets of observations have spurred interest in the function of retinoids with respect to development and disease of hematopoietic cells. Since the 1920s, epidemiological studies indicated altered hematopoiesis in vitamin A-deficient (VAD) human populations. More recently, the ability of retinoids to affect various aspects of hematopoietic development has been demonstrated in vitro. Finally, it was discovered that the gene encoding a retinoid receptor is a key target for chromosomal translocations that cause acute promyelocytic leukemia (APL). More recent investigations using targeted gene disruptions, VAD animal models, and mouse models of leukemia have continued to shed light on the function of the retinoid pathway in blood cells. It is now clear that retinoids are required for normal hematopoiesis during both yolk sac and fetal liver stages of hematopoiesis, while the pathway has at least modulatory functions for bone marrow derived progenitors. Studies of normal development and APL have provided complementary insight into the molecular control of blood cell differentiation. Here we review the evidence for retinoid requirements in hematopoiesis and also summarize current ideas regarding how this pathway is subverted in leukemia.
authors.affiliation: Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Chanin 501, Bronx, NY 10461, USA.
authors.forename: Tal
authors.initials: T
authors.lastname: Oren
authors.forename: Justin A
authors.initials: JA
authors.lastname: Sher
authors.forename: Todd
authors.initials: T
authors.lastname: Evans
mesh_terms: D000818:Animals; D002869:Chromosome Aberrations; D005314:Embryonic and Fetal Development / Q000187:drug effects / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000517:prevention & control; D018168:Receptors, Retinoic Acid / Q000502:physiology; D012176:Retinoids / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014178:Translocation, Genetic; D014801:Vitamin A; D014802:Vitamin A Deficiency; D015017:Yolk Sac / Q000196:embryology
chemical_list: D018168:Receptors, Retinoic Acid; D012176:Retinoids; D014801:Vitamin A