Marked genetic heterogeneity in familial myelodysplasia/acute myeloid leukaemia

Br J Haematol. 2012 Jul;158(2):242-248. doi: 10.1111/j.1365-2141.2012.09136.x. Epub 2012 Apr 26.


The myelodysplastic syndromes (MDS) are heterogeneous and can evolve into acute myeloid leukaemia (AML). Rare familial cases are reported in which five disease genes have been identified to date (RUNX1, CEBPA, TERC, TERT and GATA2). Here we report the genetic categorization of 27 families with familial MDS/AML. All of these families were screened for RUNX1, CEBPA, TERC, TERT and GATA2 as well as TET2 and NPM1. Five of the 27 families had telomerase mutations; one had a RUNX1 mutation, while none were found to have TET2, CEBPA or NPM1 mutations. We identified four families with heterozygous GATA2 mutations, each associated with a different phenotype. While one of these mutations is novel, three have been previously reported: one has been described in dendritic cell, monocyte, B and NK lymphoid (DCML) deficiency and one is in a family that has been reported in a series with primary lymphoedema with a predisposition to AML (Emberger syndrome). In summary, genetic characterization was shown in 10 (four GATA2, three TERT, two TERC, one RUNX1) of these families; however 17 remain uncharacterized, highlighting marked genetic heterogeneity in familial MDS/AML and the scope for further functional pathways that could give rise to this group of disorders.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Chromatography, High Pressure Liquid / methods
  • DNA, Neoplasm / genetics
  • GATA2 Transcription Factor / genetics
  • Genes, Neoplasm
  • Genetic Predisposition to Disease
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Middle Aged
  • Mutation
  • Myelodysplastic Syndromes / genetics*
  • Nucleophosmin
  • Pedigree
  • Phenotype
  • Young Adult


  • DNA, Neoplasm
  • GATA2 Transcription Factor
  • GATA2 protein, human
  • NPM1 protein, human
  • Nucleophosmin