Germ-line GATA2 p.THR354MET mutation in familial myelodysplastic syndrome with acquired monosomy 7 and ASXL1 mutation demonstrating rapid onset and poor survival

Csaba Bödör, Aline Renneville, Matthew Smith, Aurélie Charazac, Sameena Iqbal, Pascaline Étancelin, Jamie Cavenagh, Michael J. Barnett, Karolina Kramarzová, Biju Krishnan, András Matolcsy, Claude Preudhomme, Jude Fitzgibbon, Carolyn Owen

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58 Citations (Scopus)

Abstract

While most myelodysplastic syndrome/acute myeloid leukemia cases are sporadic, rare familial cases occur and provide some insight into leukemogenesis. The most clearly defined familial cases result from inherited mutations in RUNX1 or CEBPA. Recently, novel germline mutations in GATA2 have been reported. We, therefore, investigated individuals from families with one or more first-degree relatives with myelodysplastic syndrome/acute myeloid leukemia with wild-type RUNX1 and CEBPA, for GATA2 mutations. Screening for other recurrent mutations was also performed. A GATA2 p.Thr354Met mutation was observed in a pedigree in which 2 first-degree cousins developed high-risk myelodysplastic syndrome with monosomy 7. They were also observed to have acquired identical somatic ASXL1 mutations and both died despite stem cell transplantation. These findings confirm that germline GATA2 mutations predispose to familial myelodysplastic syndrome/acute myeloid leukemia, and that monosomy 7 and ASXL1 mutations may be recurrent secondary genetic abnormalities triggering overt malignancy in these families.

Original languageEnglish
Pages (from-to)890-894
Number of pages5
JournalHaematologica
Volume97
Issue number6
DOIs
Publication statusPublished - Jun 1 2012

Keywords

  • Familial
  • GATA2
  • Monosomy 7
  • Myelodysplastic syndromes

ASJC Scopus subject areas

  • Hematology

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    Bödör, C., Renneville, A., Smith, M., Charazac, A., Iqbal, S., Étancelin, P., Cavenagh, J., Barnett, M. J., Kramarzová, K., Krishnan, B., Matolcsy, A., Preudhomme, C., Fitzgibbon, J., & Owen, C. (2012). Germ-line GATA2 p.THR354MET mutation in familial myelodysplastic syndrome with acquired monosomy 7 and ASXL1 mutation demonstrating rapid onset and poor survival. Haematologica, 97(6), 890-894. https://doi.org/10.3324/haematol.2011.054361