Acquired ASXL1 mutations are common in patients with inherited GATA2 mutations and correlate with myeloid transformation
Acquired ASXL1 mutations are common in patients with inherited GATA2 mutations and correlate with myeloid transformation
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DOI：
10.3324/haematol.2013.090217
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发表时间：
2014-02-01
期刊：
影响因子：
10.1
通讯作者：
Hickstein, Dennis D.
中科院分区：
文献类型：
--
作者：
West, Robert R.;Hsu, Amy P.;Hickstein, Dennis D.
转录因子GATA 2中的遗传性或散发性杂合突变导致临床综合征，其特征在于非结核性分枝杆菌感染和其他机会性感染，单核细胞、B细胞和自然杀伤细胞的严重缺乏，以及从细胞减少型骨髓增生异常综合征进展为骨髓性白血病。为了鉴定与GATA 2突变患者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转化为髓系白血病相关的ASXL 1基因区域进行了测序。在14/48例（29%）GATA 2缺乏症患者中发现了体细胞杂合ASXL 1突变，其中包括5例发生增殖性慢性粒单核细胞白血病的患者中的4例。尽管与先前描述的ASXL 1突变患者相比，GATA 2突变患者的髓系转化发生率相似，但获得性ASXL 1突变的GATA 2缺陷患者相当年轻，几乎完全是女性，并且转化为增殖性慢性粒单核细胞白血病的发生率很高。这些患者在发生急性髓细胞性白血病或慢性粒单核细胞性白血病之前，可从异基因造血干细胞移植中获益。
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.