The evolution of cellular deficiency in GATA2 mutation

Research output: Contribution to journalArticlepeer-review


  • Rachel E Dickinson
  • Paul Milne
  • Laura Jardine
  • Sasan Zandi
  • Sabina I Swierczek
  • Naomi McGovern
  • Sharon Cookson
  • Zaveyna Ferozepurwalla
  • Alexander Langridge
  • Sarah Pagan
  • Andrew Gennery
  • Tarja Heiskanen-Kosma
  • Sari Hämäläinen
  • Mikko Seppänen
  • Matthew Helbert
  • Eleni Tholouli
  • Eleonora Gambineri
  • Sigrún Reykdal
  • Magnús Gottfreðsson
  • James E Thaventhiran
  • Emma Morris
  • Stephen Jolles
  • Chris M Bacon
  • Sophie Hambleton
  • Muzlifah Haniffa
  • Yenan Bryceson
  • Carl Allen
  • Josef T Prchal
  • John E Dick
  • Venetia Bigley
  • Matthew Collin


Constitutive heterozygous GATA2 mutation is associated with deafness, lymphedema, mononuclear cytopenias, infection, myelodysplasia (MDS), and acute myeloid leukemia. In this study, we describe a cross-sectional analysis of 24 patients and 6 relatives with 14 different frameshift or substitution mutations of GATA2. A pattern of dendritic cell, monocyte, B, and natural killer (NK) lymphoid deficiency (DCML deficiency) with elevated Fms-like tyrosine kinase 3 ligand (Flt3L) was observed in all 20 patients phenotyped, including patients with Emberger syndrome, monocytopenia with Mycobacterium avium complex (MonoMAC), and MDS. Four unaffected relatives had a normal phenotype indicating that cellular deficiency may evolve over time or is incompletely penetrant, while 2 developed subclinical cytopenias or elevated Flt3L. Patients with GATA2 mutation maintained higher hemoglobin, neutrophils, and platelets and were younger than controls with acquired MDS and wild-type GATA2. Frameshift mutations were associated with earlier age of clinical presentation than substitution mutations. Elevated Flt3L, loss of bone marrow progenitors, and clonal myelopoiesis were early signs of disease evolution. Clinical progression was associated with increasingly elevated Flt3L, depletion of transitional B cells, CD56(bright) NK cells, naïve T cells, and accumulation of terminally differentiated NK and CD8(+) memory T cells. These studies provide a framework for clinical and laboratory monitoring of patients with GATA2 mutation and may inform therapeutic decision-making.


Original languageEnglish
Pages (from-to)863-74
Number of pages12
Issue number6
Publication statusPublished - 6 Feb 2014


  • Adolescent, Adult, Aged, Aged, 80 and over, B-Lymphocytes, Biomarkers, Case-Control Studies, Child, Child, Preschool, Clonal Evolution, Cross-Sectional Studies, Dendritic Cells, Enzyme-Linked Immunosorbent Assay, Female, Follow-Up Studies, GATA2 Transcription Factor, Genetic Association Studies, Humans, Killer Cells, Natural, Male, Middle Aged, Monocytes, Mutation, Myelodysplastic Syndromes, Pedigree, Prognosis, Young Adult, fms-Like Tyrosine Kinase 3