title: Loss of B cells and their precursors is the most constant feature of GATA-2 deficiency in childhood myelodysplastic syndrome.
abstract: GATA-2 deficiency was recently described as common cause of overlapping syndromes of immunodeficiency, lymphedema, familiar myelodysplastic syndrome or acute myeloid leukemia. The aim of our study was to analyze bone marrow and peripheral blood samples of children with myelodysplastic syndrome or aplastic anemia to define prevalence of the GATA2 mutation and to assess whether mutations in GATA-2 transcription factor exhibit specific immunophenotypic features. The prevalence of a GATA2 mutation in a consecutively diagnosed cohort of children was 14% in advanced forms of myelodysplastic syndrome (refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and myelodysplasia-related acute myeloid leukemia), 17% in refractory cytopenia of childhood, and 0% in aplastic anemia. In GATA-2-deficient cases, we found the most profound B-cell lymphopenia, including its progenitors in blood and bone marrow, which correlated with significantly diminished intronRSS-Kde recombination excision circles in comparison to other myelodysplastic syndrome/aplastic anemia cases. The other typical features of GATA-2 deficiency (monocytopenia and natural killer cell lymphopenia) were less discriminative. In conclusion, we suggest screening for GATA2 mutations in pediatric myelodysplastic syndrome, preferentially in patients with impaired B-cell homeostasis in bone marrow and peripheral blood (low number of progenitors, intronRSS-Kde recombination excision circles and naïve cells).
authors.affiliation: CLIP-Department of Pediatric Hematology and Oncology, 2 Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Nováková
authors.affiliation: CLIP-Department of Pediatric Hematology and Oncology, 2 Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Markéta
authors.initials: M
authors.lastname: Žaliová
authors.affiliation: Department of Pediatric Hematology and Oncology, 2 Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Suková
authors.affiliation: Center for Pediatrics and Adolescent Medicine, University Medical Center, Freiburg, Germany.
authors.forename: Marcin
authors.initials: M
authors.lastname: Wlodarski
authors.affiliation: Center for Pediatrics and Adolescent Medicine, University Medical Center, Freiburg, Germany.
authors.forename: Aleš
authors.initials: A
authors.lastname: Janda
authors.affiliation: CLIP-Department of Pediatric Hematology and Oncology, 2 Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic Department of Pediatric Hematology and Oncology, 2 Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Froňková
authors.affiliation: Department of Pathology and Molecular Medicine, University Hospital Motol, Prague, Czech Republic.
authors.forename: Vít
authors.initials: V
authors.lastname: Campr
authors.affiliation: Department of Pediatrics, Charles University, University Hospital Hradec Králové, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Lejhancová
authors.affiliation: Department of Pediatric Hematology, Children's University Hospital, Brno, Czech Republic.
authors.forename: Ondřej
authors.initials: O
authors.lastname: Zapletal
authors.affiliation: Department of Pediatrics, Palacky University and University Hospital Olomouc, Czech Republic.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Pospíšilová
authors.affiliation: Department of Pediatrics, University Hospital Pilsen, Czech Republic.
authors.forename: Zdeňka
authors.initials: Z
authors.lastname: Černá
authors.affiliation: Department of Pediatrics Ostrava, University Hospital Ostrava, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Kuhn
authors.affiliation: Department of Pediatric Hematology and Oncology, University Hospital Bratislava, Slovakia.
authors.forename: Peter
authors.initials: P
authors.lastname: Švec
authors.affiliation: CLIP-Department of Pediatric Hematology and Oncology, 2 Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Vendula
authors.initials: V
authors.lastname: Pelková
authors.affiliation: Centre of Oncocytogenetics, Institute of Clinical Biochemistry and Laboratory Diagnostics, 1 Faculty of Medicine and General University Hospital and Charles University, Prague, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Zemanová
authors.affiliation: Department of Pathology, Aarhus University Hospital, Denmark.
authors.forename: Gitte
authors.initials: G
authors.lastname: Kerndrup
authors.affiliation: Department of Pediatric Oncology, Princess Máxima Centre for Paediatric Oncology, Utrecht, the Netherlands.
authors.forename: Marry
authors.initials: M
authors.lastname: van den Heuvel-Eibrink
authors.affiliation: Department of Immunology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Vincent
authors.initials: V
authors.lastname: van der Velden
authors.affiliation: Center for Pediatrics and Adolescent Medicine, University Medical Center, Freiburg, Germany.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Niemeyer
authors.affiliation: CLIP-Department of Pediatric Hematology and Oncology, 2 Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Kalina
authors.affiliation: CLIP-Department of Pediatric Hematology and Oncology, 2 Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic Department of Pediatric Hematology and Oncology, 2 Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Trka
authors.affiliation: Department of Pediatric Hematology and Oncology, 2 Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Starý
authors.affiliation: CLIP-Department of Pediatric Hematology and Oncology, 2 Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic Department of Pediatric Hematology and Oncology, 2 Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Ondřej
authors.initials: O
authors.lastname: Hrušák
authors.affiliation: CLIP-Department of Pediatric Hematology and Oncology, 2 Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic Department of Pediatric Hematology and Oncology, 2 Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic ester.mejstrikova@lfmotol.cuni.cz.
authors.forename: Ester
authors.initials: E
authors.lastname: Mejstříková
mesh_terms: D000293:Adolescent; D000741:Anemia, Aplastic / Q000175:diagnosis / Q000209:etiology; D001402:B-Lymphocytes / Q000378:metabolism*; D015415:Biomarkers; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D050989:GATA2 Transcription Factor / Q000172:deficiency*; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000175:diagnosis; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000175:diagnosis* / Q000235:genetics*; D022423:Myeloid Cells / Q000378:metabolism; D010641:Phenotype; D054448:Precursor Cells, B-Lymphoid / Q000378:metabolism*; D012372:ROC Curve; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D050989:GATA2 Transcription Factor