title: The role of promyelocytic leukemia zinc finger and promyelocytic leukemia in leukemogenesis and development.
abstract: Acute promyelocytic leukemia (APL) was originally distinguished by an extremely poor clinical outcome. In the past few years, however, important progress has been made in defining the molecular basis of APL pathogenesis and in optimizing its treatment to an extent that this leukemia is now considered curable. Two features are unique to this leukemia: its remission after retinoic acid (RA) treatment through induction of blast differentiation, and the presence in the leukemic blast of fusion proteins in which the retinoic acid receptor alpha (RARalpha) fuses to distinct partners. Here we review how a detailed analysis of the functions of two of these RARalpha partners, the promyelocytic leukemia (PML) and promyelocytic leukemia zinc finger (PLZF) proteins, has allowed a greater understanding of the molecular mechanisms implicated in APL pathogenesis.
authors.affiliation: Molecular Biology Program, Department of Pathology, Memorial Sloan-Kettering Cancer Center, Cornell University, New York, NY 10021, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Costoya
authors.forename: P P
authors.initials: PP
authors.lastname: Pandolfi
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D015473:Leukemia, Promyelocytic, Acute / Q000209:etiology* / Q000235:genetics; D051379:Mice; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000502:physiology*; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion / Q000502:physiology; D000071156:Promyelocytic Leukemia Protein; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D014157:Transcription Factors / Q000502:physiology*; D025521:Tumor Suppressor Proteins
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; C118318:PLZF-RARalpha fusion protein, human; C492209:PLZF-RARalpha fusion protein, mouse; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C513267:Zbtb16 protein, mouse; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; C070576:PML protein, human; C092037:ZBTB16 protein, human