Haematologica. 2014 Feb;99(2):276-81. doi: 10.3324/haematol.2013.090217. Epub 2013 Sep 27.
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. (ClinicalTrials.gov identifier NCT00018044, NCT00404560, NCT00001467, NCT00923364.).
转录因子 GATA2 的遗传性或散发性杂合突变导致一种临床综合征，其特征为非结核分枝杆菌和其他机会性感染、单核细胞、B 细胞和自然杀伤细胞严重缺乏，以及从低细胞性骨髓增生异常综合征进展为髓系白血病。为了鉴定与 GATA2 突变患者的髓系转化相关的获得性体细胞突变，我们对先前与骨髓增生异常综合征向髓系白血病转化相关的 ASXL1 基因区域进行了测序。在 48 名 GATA2 缺乏症患者中有 14 名（29%）存在 ASXL1 体细胞杂合突变，其中 5 名发生增生性慢性粒单核细胞白血病的患者中有 4 名存在 ASXL1 突变。虽然与先前描述的具有 ASXL1 突变的患者相比，GATA2 突变患者的髓系转化发生率同样较高，但具有获得性 ASXL1 突变的 GATA2 缺乏症患者年龄明显较小，几乎全部为女性，且向增生性慢性粒单核细胞白血病转化的发生率较高。这些患者可能受益于在发生急性髓系白血病或慢性粒单核细胞白血病之前进行同种异体造血干细胞移植。（ClinicalTrials.gov 标识符：NCT00018044、NCT00404560、NCT00001467、NCT00923364）。
