title: Morphologic and GATA1 sequencing analysis of hematopoiesis in fetuses with trisomy 21.
abstract: Trisomy 21 alters fetal liver hematopoiesis and, in combination with somatic globin transcription factor 1 (GATA1) mutations, leads to development of transient myeloproliferative disease in newborns. However, little is known about the morphological hematopoietic changes caused by trisomy 21 in the fetus, and to date, the exact onset of GATA1 mutations remains uncertain. Therefore, we analyzed fetal liver hematopoiesis from second trimester pregnancies in trisomy 21 and screened for GATA1 mutations. We examined 57 formalin-fixed and paraffin-embedded fetal liver specimens (49 harboring trisomy 21 and 8 controls) by immunohistochemistry for CD34, CD61, factor VIII, and glycophorin A. GATA1 exon 2 was sequenced in fetal livers and corresponding nonhematologic tissue. Cell counts of megakaryocytes (P = .022), megakaryocytic precursors (P = .021), and erythroid precursors were higher in trisomy 21 cases. CD34-positive hematopoietic blasts showed no statistically significant differences. No mutation was detected by GATA1 exon 2 sequencing in fetal livers from 12 to 25 weeks of gestation. Our results suggest that GATA1 exon 2 mutations occur late in trisomy 21 fetal hematopoiesis. However, trisomy 21 alone provides a proliferative stimulus of fetal megakaryopoiesis and erythropoiesis. CD34-positive precursor cells are not increased in trisomy 21 fetal livers.
authors.affiliation: Department of Pathology, Hospital of the University of Basel, Basel, Switzerland. Electronic address: hoellers@uhbs.ch.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Hoeller
authors.affiliation: Department of Pathology, Hospital of the University of Basel, Basel, Switzerland.
authors.forename: Michel P
authors.initials: MP
authors.lastname: Bihl
authors.affiliation: Department of Pathology, Hospital of the University of Basel, Basel, Switzerland.
authors.forename: Alexandar
authors.initials: A
authors.lastname: Tzankov
authors.affiliation: Department of Pathology, Hospital of the University of Basel, Basel, Switzerland.
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Chaffard
authors.affiliation: Department of Pathology, Hospital of the University of Basel, Basel, Switzerland.
authors.forename: Petra
authors.initials: P
authors.lastname: Hirschmann
authors.affiliation: University Children's Hospital, Medical Genetics, Basel, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Miny
authors.affiliation: Department of Paediatrics, Oncology/Hematology, University Children's Hospital, Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kühne
authors.affiliation: Department of Pathology, Hospital of the University of Basel, Basel, Switzerland.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bruder
mesh_terms: D004314:Down Syndrome / Q000196:embryology / Q000235:genetics*; D005260:Female; D050982:GATA1 Transcription Factor / Q000235:genetics*; D006410:Hematopoiesis / Q000235:genetics*; D006801:Humans; D007947:Leukemia, Megakaryoblastic, Acute / Q000235:genetics; D008099:Liver / Q000196:embryology; D008297:Male; D008533:Megakaryocytes / Q000502:physiology; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D034061:Thrombopoiesis / Q000235:genetics
chemical_list: D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human
keywords: Fetal; GATA1; Hematopoiesis; Megakaryoblastic leukaemia; Trisomy 21