title: Acute promyelocytic leukemia: PML/RARalpha and the leukemic stem cell.
abstract: Acute promyelocytic leukemia (APL) is distinguished from other acute myeloid leukemias (AMLs) by cytogenetic, clinical, as well as biological characteristics. The hallmark of APL is the t(15;17), which leads to the expression of the PML/RARalpha fusion protein. PML/RARalpha is the central leukemia-inducing lesion in APL and is directly targeted by all trans retinoic acid (t-RA) as well as by arsenic, both compounds able to induce complete remissions. This review focuses on potential stem cell involvement in APL outlining the knowledge about the APL-initiating stem cell and the influence of PML/RARalpha on the biology of the hematopoietic stem cell. Moreover, the importance of the blockage of t-RA signaling by the PML/RARalpha for the pathogenesis of APL is discussed, taking the relevance of the t-RA signaling pathway for the global hematopoiesis into account.
authors.affiliation: Med. Klinik III/Abtl. Hämatologie, Labor für Experimentelle Hämatologie, Johann Wolfgang Goethe-Universität, Frankfurt, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Puccetti
authors.forename: M
authors.initials: M
authors.lastname: Ruthardt
mesh_terms: D017209:Apoptosis; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D009363:Neoplasm Proteins / Q000502:physiology*; D014411:Neoplastic Stem Cells / Q000502:physiology*; D015514:Oncogene Proteins, Fusion / Q000502:physiology*; D015398:Signal Transduction; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin