MSI2 protein expression predicts unfavorable outcome in acute myeloid leukemia
MSI2 protein expression predicts unfavorable outcome in acute myeloid leukemia
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DOI：
10.1182/blood-2011-04-346767
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发表时间：
2011-09-08
期刊：
影响因子：
20.3
通讯作者：
Kutok, Jeffery L.
中科院分区：
文献类型：
--
作者：
Byers, Richard J.;Currie, Treeve;Kutok, Jeffery L.
MSI2在人髓系白血病(AML)细胞系中高表达，其高表达与AML患者生存率降低有关，提示其可作为一种新的预后标志物。为了验证这一点，我们用免疫组织化学方法检测了120例AML患者的MSI2蛋白水平。大多数病例(70%)显示一定程度的胞核或胞浆阳性，但大多数病例的阳性细胞比例较低。尽管如此，MSI2蛋白的表达与预后呈负相关，特别是对于细胞遗传学亚群良好的患者。出于实际诊断的目的，相关性最强的是有1%的细胞显示出很强的MSI2染色，这些细胞的预后非常差(P<；.0001)。结合细胞遗传学分类、年龄、白细胞计数和法美英亚型的多变量分析表明，核MSI2水平独立预测预后(P=.0497)。这些结果在蛋白水平上证实了MSI2的表达与AML预后的关系，并证明了MSI2蛋白作为临床预后生物标志物的实用性。此外，尽管在大多数情况下在一定程度上呈阳性，但其预后能力来自于少数阳性细胞，支持其在控制正常造血干细胞功能方面的作用，并突出其在疾病进展中的作用。(血。2011；118(10)：2857-2867)
MSI2 is highly expressed in human myeloid leukemia (AML) cell lines, and high expression of MSI2 mRNA is associated with decreased survival in AML, suggesting its use as a new prognostic marker. To test this, we measured MSI2 protein level by immunohistochemistry in 120 AML patients. Most cases (70%) showed some nuclear or cytoplasmic positivity, but the percentage of positive cells was low in most cases. Despite this, MSI2 protein expression was negatively associated with outcome, particularly for patients with good cytogenetic subgroup. For practical diagnostic purposes, the strongest significance of association was seen in cases with > 1% of cells showing strong MSI2 staining, these having a very poor outcome (P < .0001). Multivariate analysis with cytogenetic category, age, white cell count, and French-American-British subtype demonstrated that nuclear MSI2 levels were independently predictive of outcome (P = .0497). These results confirm the association of MSI2 expression with outcome in AML at the protein level and demonstrate the utility of MSI2 protein as a clinical prognostic biomarker. In addition, although positive at some level in most cases, its prognostic power derived from few positive cells, supporting its role in control of normal hematopoietic stem cell function and highlighting its role in disease progression. (Blood. 2011; 118(10): 2857-2867)