Copy Number Variations of EphA3 Are Associated With Multiple Types of Hematologic Malignancies
Copy Number Variations of EphA3 Are Associated With Multiple Types of Hematologic Malignancies
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DOI：
10.3816/clml.2011.n.006
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发表时间：
2011-02-01
影响因子：
2.7
通讯作者：
Zhang, Wei
中科院分区：
文献类型：
--
作者：
Guan, Ming;Liu, Li;Zhang, Wei
背景：EphA3 是 Eph 受体家族的一个组成部分，Eph 受体家族是受体酪氨酸激酶 (RTK) 家族最大的亚群。最近的一项基于芯片的研究表明急性髓性白血病基因组中存在 EphA3 拷贝数变异 (CNV)。 CNV 不同程度地存在于普通人群中，并且已被发现与包括血液恶性肿瘤在内的多种类型的疾病相关。然而，目前的研究大多集中在CNV的全基因组筛选上，这些区域的功能影响需要在大量临床样本中进行广泛研究。患者和方法：在我们的研究中，我们收集了来自多种类型血液恶性肿瘤以及健康对照的 617 份骨髓样本。检查了这些样本中 EphA3 的 DNA 拷贝数和 mRNA 水平。结果：我们发现 EphA3 的 CNV 与这些血液恶性肿瘤之间存在显着相关性，包括急性淋巴细胞白血病 (ALL)、急性粒细胞白血病 (AML)、慢性淋巴细胞白血病 (CLL)、慢性粒细胞白血病 (CML)、多发性骨髓瘤 (MM) 和骨髓增生异常综合征 (MDS)。我们还观察到 EphA3 的相对 mRNA 水平与基因剂量之间呈正相关。结论：EphA3的CNV与多种类型的血液恶性肿瘤相关，包括ALL、AML、CLL、CML、MM和MDS。
Background: EphA3 is a component of the Eph receptor family, the largest subgroup of the receptor tyrosine kinase (RTK) family. A recent array-based study implicated the presence of copy-number variations (CNVs) of EphA3 in the genomes of acute myelogenous leukemia. CNVs are present in the general population at varying degrees, and have been found to associate with various types of diseases including hematologic malignancies. However, most of the current studies focused on the genome-wide screening of CNVs, and the functional impact of such regions needs to be extensively investigated in large number of clinical samples. Patients and Methods: In our study, we collected 617 bone marrow samples from multiple types of hematologic malignancies as well as healthy controls. DNA copy numbers and mRNA levels of EphA3 in these samples were examined. Results: We found significant association between the CNVs of EphA3 and these hematologic malignancies including acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), multiple myeloma (MM), and myelodysplastic syndrome (MDS). We also observed a positive correlation between the relative mRNA level and gene dosage of EphA3. Conclusion: The CNVs of EphA3 were associated with multiple types of hematologic malignancies including ALL, AML, CLL, CML, MM, and MDS.