Acquired ASXL1 mutations are common in patients with inherited GATA2 mutations and correlate with myeloid transformation

被引:113
作者
West, Robert R. [1 ]
Hsu, Amy P. [2 ]
Holland, Steven M. [2 ]
Cuellar-Rodriguez, Jennifer [2 ]
Hickstein, Dennis D. [1 ]
机构
[1] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
[2] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
CHRONIC MYELOMONOCYTIC LEUKEMIA; FAMILIAL MYELODYSPLASTIC SYNDROME; PROGNOSTIC MODEL; SPORADIC MONOCYTOPENIA; AUTOSOMAL-DOMINANT; SRSF2; MUTATIONS; PROSTATE-CANCER; POOR-PROGNOSIS; GENE-MUTATIONS; AML;
D O I
10.3324/haematol.2013.090217
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Inherited or sporadic heterozygous mutations in the transcription factor GATA2 lead to a clinical syndrome characterized by non-tuberculous mycobacterial and other opportunistic infections, a severe deficiency in monocytes, B cells and natural killer cells, and progression from a hypocellular myelodysplastic syndrome to myeloid leukemias. To identify acquired somatic mutations associated with myeloid transformation in patients with GATA2 mutations, we sequenced the region of the ASXL1 gene previously associated with transformation from myelodysplasia to myeloid leukemia. Somatic, heterozygous ASXL1 mutations were identified in 14/48 (29%) of patients with GATA2 deficiency, including four out of five patients who developed a proliferative chronic myelomonocytic leukemia. Although patients with GATA2 mutations had a similarly high incidence of myeloid transformation when compared to previously described patients with ASXL1 mutations, GATA2 deficiency patients with acquired ASXL1 mutation were considerably younger, almost exclusively female, and had a high incidence of transformation to a proliferative chronic myelomonocytic leukemia. These patients may benefit from allogeneic hematopoietic stem cell transplantation before the development of acute myeloid leukemia or chronic myelomonocytic leukemia.
引用
收藏
页码:276 / 281
页数:6
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