High frequency of GATA2 mutations in patients with mild chronic neutropenia evolving to MonoMac syndrome, myelodysplasia, and acute myeloid leukemia

Blood. 2013 Jan 31;121(5):822-9. doi: 10.1182/blood-2012-08-447367. Epub 2012 Dec 6.


Congenital neutropenia is a group of genetic disorders that involve chronic neutropenia and susceptibility to infections. These neutropenias may be isolated or associated with immunologic defects or extra-hematopoietic manifestations. Complications may occur as infectious diseases, but also less frequently as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Recently, the transcription factor GATA2 has been identified as a new predisposing gene for familial AML/MDS. In the present study, we describe the initial identification by exome sequencing of a GATA2 R396Q mutation in a family with a history of chronic mild neutropenia evolving to AML and/or MDS. The subsequent analysis of the French Severe Chronic Neutropenia Registry allowed the identification of 6 additional pedigrees and 10 patients with 6 different and not previously reportedGATA2 mutations (R204X, E224X, R330X, A372T, M388V, and a complete deletion of the GATA2 locus). The frequent evolution to MDS and AML in these patients reveals the importance of screening GATA2 in chronic neutropenia associated with monocytopenia because of the frequent hematopoietic transformation, variable clinical expression at onset, and the need for aggressive therapy in patients with poor clinical outcome.

Key points: Mutations of key transcription factor in myeloid malignancies.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Substitution
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Child
  • Child, Preschool
  • Female
  • France
  • GATA2 Transcription Factor / genetics*
  • GATA2 Transcription Factor / metabolism
  • Genetic Diseases, Inborn / genetics*
  • Genetic Diseases, Inborn / metabolism
  • Genetic Diseases, Inborn / pathology
  • Genetic Diseases, Inborn / therapy
  • Genetic Loci
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Mutation, Missense*
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / metabolism
  • Myelodysplastic Syndromes / pathology
  • Myelodysplastic Syndromes / therapy
  • Neutropenia / genetics*
  • Neutropenia / metabolism
  • Pedigree
  • Registries


  • GATA2 Transcription Factor
  • GATA2 protein, human