Spectrum of myeloid neoplasms and immune deficiency associated with germline GATA2 mutations.
Bottom Line: Allogeneic stem cell transplant remains the treatment of choice.Morbidity, mortality, and social costs due to the familial nature of the disease are considerable.We describe our experience with the disorder in three affected families and a comprehensive review of current literature.
Affiliation: Penn State Milton S. Hershey Cancer Institute, Hershey, Pennsylvania.Show MeSH
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Mentions: GATA2 overexpression has been documented in one-third to one half of nonfamilial AML and correlates with a poor prognosis with shorter overall and event-free survival when treated with standard chemotherapy 55,56. Of the original four families with GATA2 mutations, described by Hahn et al. with MDS/AML, three had the T354M mutation, and one had deletion T355. Both mutations occurred in the second zinc finger (ZF) of GATA2 (Fig 1). In the T354 mutation families, all members had the mutation but not all had developed hematological disease at least by the time of reporting 16. Bone marrow biopsies are typically hypocellular in contrast to the common MDS marrow picture, with abundant atypical megakaryocytes in >90% patients 53. Some patients have also fulfilled the diagnostic criteria for CMML (chronic myelomonocytic leukemia) and LGL (large granular lymphocytic leukemia) suggesting overlap syndromes 53. Other acquired mutations such as ASXL1 may herald the development of AML 57. Increased levels of FLT3 ligand have also been reported to be associated with clinical progression 58.
Affiliation: Penn State Milton S. Hershey Cancer Institute, Hershey, Pennsylvania.