GATA1 mutations in Down syndrome:: Implications for biology and diagnosis of children with transient myeloproliferative disorder and acute megakaryoblastic leukemia
GATA1 mutations in Down syndrome:: Implications for biology and diagnosis of children with transient myeloproliferative disorder and acute megakaryoblastic leukemia
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DOI：
10.1002/pbc.20066
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发表时间：
2005-01-01
影响因子：
3.2
通讯作者：
Crispino, JD
中科院分区：
文献类型：
--
作者：
Crispino, JD
虽然医生们几十年前就知道唐氏综合症患儿易患短暂性骨髓增生性疾病（TMD）和急性巨核母细胞白血病（AMKL），但关于这些疾病的许多问题仍未解决。首先，TMD和AMKL是什么关系？第二，哪些特定的基因改变导致了白血病的发生？最后，是什么因素导致这些髓系疾病的易感性增加？在这篇综述中，我将总结从最近的发现中获得的关于TMD和AMKL生物学的重要新见解，GATA1是一种编码必需造血转录因子的基因，在几乎所有这些恶性肿瘤患者的白血病原细胞中发生突变。此外，我将讨论检测GATA I突变的存在是否有助于诊断这些和相关的巨核细胞白血病。未来的研究旨在确定突变GATA-1蛋白的活性，并确定21号染色体编码的相互作用因子，这可能会使人们对这种有趣的白血病有更深入的了解。(C) 2004 Wiley-Liss, Inc。
Although physicians have known for many decades that children with Down syndrome are predisposed to developing transient myeloproliferative disorder (TMD) and acute megakaryoblastic leukemia (AMKL), many questions regarding these disorders remain unresolved. First, what is the relationship between TMD and AMKL? Second, what specific genetic alterations contribute to the leukemic process? Finally, what factors lead to the increased predisposition to these myeloid disorders? In this review I will summarize important new insights into the biology of TMD and AMKL gained from the recent discovery that GATA1, a gene that encodes an essential hematopoietic transcription factor, is Mutated in the leukemic blasts from nearly all patients with these malignancies. In addition, I will discuss whether assaying for the presence of a GATA I mutation can aid in the diagnosis of these and related megakaryoblastic leukemias. Future research aimed at defining the activity of mutant GATA-1 protein and identifying interacting factors encoded by chromosome 21 will likely lead to an even greater understanding of this intriguing leukemia. (C) 2004 Wiley-Liss, Inc.