title: Transcription factors Fli1 and EKLF in the differentiation of megakaryocytic and erythroid progenitor in 5q- syndrome and in Diamond-Blackfan anemia.
abstract: Friend leukemia virus integration 1 (Fli1) and erythroid Krüppel-like factor (EKLF) participate under experimental conditions in the differentiation of megakaryocytic and erythroid progenitor in cooperation with other transcription factors, cytokines, cytokine receptors, and microRNAs. Defective erythropoiesis with refractory anemia and effective megakaryopoiesis with normal or increased platelet count is typical for 5q- syndrome. We decided to evaluate the roles of EKLF and Fli1 in the pathogenesis of this syndrome and of another ribosomopathy, Diamond-Blackfan anemia (DBA). Fli1 and EKLF mRNA levels were examined in mononuclear blood and bone marrow cells from patients with 5q- syndrome, low-risk MDS patients with normal chromosome 5, DBA patients, and healthy controls. In 5q- syndrome, high Fli1 mRNA levels in the blood and bone marrow mononuclear cells were found. In DBA, Fli1 expression did not differ from the controls. EKLF mRNA level was significantly decreased in the blood and bone marrow of 5q- syndrome and in all DBA patients. We propose that the elevated Fli1 in 5q- syndrome protects megakaryocytic cells from ribosomal stress contrary to erythroid cells and contributes to effective though dysplastic megakaryopoiesis.
authors.affiliation: 1st Department of Medicine, Department of Hematology, General University Hospital, U Nemocnice 2, Prague 2, 128 00, Czech Republic. neuwirtova.radana@vfn.cz
authors.forename: Radana
authors.initials: R
authors.lastname: Neuwirtova
authors.forename: Ota
authors.initials: O
authors.lastname: Fuchs
authors.forename: Monika
authors.initials: M
authors.lastname: Holicka
authors.forename: Martin
authors.initials: M
authors.lastname: Vostry
authors.forename: Arnost
authors.initials: A
authors.lastname: Kostecka
authors.forename: Hana
authors.initials: H
authors.lastname: Hajkova
authors.forename: Anna
authors.initials: A
authors.lastname: Jonasova
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Cermak
authors.forename: Radek
authors.initials: R
authors.lastname: Cmejla
authors.forename: Dagmar
authors.initials: D
authors.lastname: Pospisilova
authors.forename: Monika
authors.initials: M
authors.lastname: Belickova
authors.forename: Magda
authors.initials: M
authors.lastname: Siskova
authors.forename: Ivana
authors.initials: I
authors.lastname: Hochova
authors.forename: Jana
authors.initials: J
authors.lastname: Vondrakova
authors.forename: Dana
authors.initials: D
authors.lastname: Sponerova
authors.forename: Eva
authors.initials: E
authors.lastname: Kadlckova
authors.forename: Ludmila
authors.initials: L
authors.lastname: Novakova
authors.forename: Jana
authors.initials: J
authors.lastname: Brezinova
authors.forename: Kyra
authors.initials: K
authors.lastname: Michalova
mesh_terms: D000293:Adolescent; D000328:Adult; D029503:Anemia, Diamond-Blackfan / Q000235:genetics* / Q000378:metabolism; D000748:Anemia, Macrocytic / Q000235:genetics* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D002648:Child; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics / Q000378:metabolism; D018899:CpG Islands; D004920:Erythropoiesis / Q000235:genetics*; D005260:Female; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000378:metabolism; D051789:Proto-Oncogene Protein c-fli-1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000097:blood; D060888:Real-Time Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000502:physiology; D034061:Thrombopoiesis / Q000235:genetics*; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: C078433:FLI1 protein, human; D051741:Kruppel-Like Transcription Factors; D051789:Proto-Oncogene Protein c-fli-1; D012333:RNA, Messenger; D012269:Ribosomal Proteins; C080774:erythroid Kruppel-like factor