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Blood: 鸡生蛋or蛋生鸡?MDS or AML?

来源:生物谷 2015-03-02 18:13

2015年3月2日 讯/生物谷BIOON/--骨髓增生异常综合征(MDS)是一组异质性后天性克隆性疾病,其基本病变是克隆性造血干/祖细胞发育异常,导致无法造血以及恶性转化危险性增高。表现为骨髓中各造血细胞数量增多或正常,外周血中各系血细胞明显减少。而且有可能演变为急性髓系白血病(AML)。近日,来自美国华盛顿大学的Lindsley团队对于是否MDS会导致AML进行了研究,并鉴别出8个突变基因会导致易患继发性AML。

 
如果没有过度的骨髓发育不良或者骨髓疾病的病史,AML患者是原发性还是继发性通常是很难判断的,尤其是对于年纪较大的患者。然而,这两者的鉴别诊断非常关键,因为如果是由MDS恶性转化为AML,通常意味着预后不良。Lindsley团队试图研究原发性和继发性AML之间的基因突变情况有何不同,能为临床转归做出任何提示。研究结果发现,有8个基因突变与继发性AML高度相关。那些被诊断为原发性AML的老年患者如果有这8个基因的突变常伴随预后不良。这些研究结果表明预后不良的原发性AML患者的确存在一些特异性的基因突变,这也解释了我们在AML患者中发现的临床异质性。
 
Lindsley团队选择了93名继发性AML的患者作为研究对象,对他们的基因序列进行筛查。实验结果发现SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, STAG2等8个基因的突变特异性的出现于继发性AML患者。同时,作者还找到一些在原发性AML患者中突变频率较高的基因。最后,作者还发现TP53突变的AML患者预后最差。(生物谷Bioon.com)
 
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What came first: MDS or AML?
 
Matthew J.Walter
 
In this issue of Blood, Lindsley et al have identified a set of 8 genes that, when mutated, appear to be highly specific for secondary acute myeloid leukemia (AML) vs de novo AML.1
 
In the absence of overt bone marrow dysplasia or a prior history of a myeloid disease, it is not always clear whether a patient has de novo or secondary AML, especially for elderly patients. This is an important distinction, because patients with secondary AML arising from an antecedent myelodysplastic syndrome (MDS) have worse outcomes compared with de novo AML patients. Can gene mutations present at the time of AML diagnosis distinguish between secondary vs de novo AML and be predictive of clinical outcomes? Lindsley et al identified a set of 8 genes that appear to be highly specific for secondary AML vs de novo AML when mutated.1 Mutations in these 8 genes define a secondary AML-like disease in elderly patients who have clinically defined de novo AML that is associated with worse clinical outcomes. These findings suggest that the presence of specific gene mutations may identify a subset of de novo AML patients with poor outcomes and explain some of the clinical heterogeneity we observe in AML.
 
Lindsley et al evaluated sequence variants within a panel of genes in a well-annotated set of 93 patients with secondary AML who were defined by the histologic documentation of antecedent MDS or chronic myelomonocytic leukemia according to the World Health Organization criteria, at least 3 months prior to study entry. By comparing the mutation frequency of recurrently mutated genes in secondary AML cases vs 180 non-M3 de novo AML patients from The Cancer Genome Atlas cohort,2 they showed that mutations in SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2 were 95% specific for the diagnosis of secondary AML (called secondary-type mutations). They also defined a set of genes that were more frequently mutated in de novo AML, or that had similar mutation frequencies between the 2 cohorts (de novo/pan-AML mutations). Finally, patients with TP53 mutations defined a third set of AML patients that had the worst outcomes, confirming previous studies.3 Lindsley et al found that the presence of secondary-type or de novo/pan-AML mutations were predictive of clinical outcomes.
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