title: GATA2 deficiency-associated bone marrow disorder differs from idiopathic aplastic anemia.
abstract: Germ-line GATA2 gene mutations, leading to haploinsufficiency, have been identified in patients with familial myelodysplastic syndrome/acute myeloid leukemia, monocytopenia and mycobacterial infections, Emberger syndrome, and dendritic cell, monocyte, B-, and NK-cell deficiency. GATA2 mutations have also been reported in a minority of patients with congenital neutropenia and aplastic anemia (AA). The bone marrow (BM) from patients with GATA2 deficiency is typically hypocellular, with varying degrees of dysplasia. Distinguishing GATA2 patients from those with AA is critical for selecting appropriate therapy. We compared the BM flow cytometric, morphologic, and cytogenetic features of 28 GATA2 patients with those of 32 patients being evaluated for idiopathic AA. The marrow of GATA2 patients had severely reduced monocytes, B cells, and NK cells; absent hematogones; and inverted CD4:CD8 ratios. Atypical megakaryocytes and abnormal cytogenetics were more common in GATA2 marrows. CD34(+) cells were comparably reduced in GATA2 and AA. Using these criteria, we prospectively identified 4 of 32 patients with suspected AA who had features suspicious for GATA2 mutations, later confirmed by DNA sequencing. Our results show that routine BM flow cytometry, morphology, and cytogenetics in patients who present with cytopenia(s) can identify patients for whom GATA2 sequencing is indicated.
authors.affiliation: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD;
authors.forename: Karthik A
authors.initials: KA
authors.lastname: Ganapathi
authors.affiliation: Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD;
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Townsley
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;
authors.forename: Amy P
authors.initials: AP
authors.lastname: Hsu
authors.affiliation: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD;
authors.forename: Diane C
authors.initials: DC
authors.lastname: Arthur
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;
authors.forename: Christa S
authors.initials: CS
authors.lastname: Zerbe
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cuellar-Rodriguez
authors.affiliation: Experimental Transplantation and Immunology, National Cancer Institute, National Institutes of Health, Bethesda, MD;
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Hickstein
authors.affiliation: Immunology Section, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD; and.
authors.forename: Sergio D
authors.initials: SD
authors.lastname: Rosenzweig
authors.affiliation: Hematology Section, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD.
authors.forename: Raul C
authors.initials: RC
authors.lastname: Braylan
authors.affiliation: Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD;
authors.forename: Neal S
authors.initials: NS
authors.lastname: Young
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
authors.affiliation: Hematology Section, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD.
authors.forename: Katherine R
authors.identifier: http://orcid.org/0000-0002-0771-4191
authors.initials: KR
authors.lastname: Calvo
mesh_terms: D000328:Adult; D000741:Anemia, Aplastic / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D001853:Bone Marrow / Q000473:pathology; D001855:Bone Marrow Diseases / Q000175:diagnosis* / Q000235:genetics; D015331:Cohort Studies; D003582:Cytogenetics; D005260:Female; D005434:Flow Cytometry; D050989:GATA2 Transcription Factor / Q000172:deficiency*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human