肌相关基因 MYF6 在毛细胞白血病中的表达。
Expression of the muscle-associated gene MYF6 in hairy cell leukemia.
机构信息
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD , United States of America.
Cancer Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America.
出版信息
PLoS One. 2020 Feb 10;15(2):e0227586. doi: 10.1371/journal.pone.0227586. eCollection 2020.
Hairy cell leukemia (HCL) is a purine analog-responsive B-cell malignancy containing the BRAF V600E mutation, expressing CD22, CD11c, CD103, tartrate resistant acid phosphatase (TRAP) CD25, CD123, and annexin 1A. BRAF V600E and the latter 4 markers are usually absent in the more aggressive and chemoresistant variant HCLv. To evaluate differences between HCL and HCLv, expression microarrays comparing HCL with HCLv were performed for 24694 genes using 47323 probes. Microarray data from 35 HCL and 27 HCLv purified samples showed the greatest HCL-HCLv difference in the muscle-associated gene MYF6, expressed by its 2 probes 18.5- and 10.8-fold higher in HCL than HCLv (p<0.0001). By real-time quantitative PCR (RQ-PCR), 100% of 152 classic HCL samples were MYF6-positive, vs 5 (6%) of 90 blood donors. MYF6-expression was also detected in 18 (35%) of 51 with HCLv, 11 (92%) of 12 with HCL expressing unmutated IGHV4-34, 35 (73%) of 48 with chronic lymphocytic leukemia (CLL), and 1 (8%) of 12 with mantle cell lymphoma. Hypomethylation status of MYF6 supported expression in HCL more than HCLv. Posttreatment blood samples becoming negative by flow cytometry remained MYF6+ by RQ-PCR in 42 (48%) of 87 HCL patients, and MYF6 RQ-PCR could detect 1 HCL in 105 normal cells. MYF6, universally expressed in HCL and in most CLL samples, may be a useful biomarker for these leukemias. Further studies are underway to determine the role of MYF6 in HCL.
毛细胞白血病（HCL）是一种嘌呤类似物反应性 B 细胞恶性肿瘤，含有 BRAF V600E 突变，表达 CD22、CD11c、CD103、抗酒石酸酸性磷酸酶（TRAP）、CD25、CD123 和膜联蛋白 1A。BRAF V600E 和后 4 种标志物通常不存在于侵袭性更强和更耐药的 HCLv 变体中。为了评估 HCL 和 HCLv 之间的差异，使用 47323 个探针对 24694 个基因进行了比较 HCL 和 HCLv 的表达微阵列分析。来自 35 例 HCL 和 27 例 HCLv 纯化样本的微阵列数据显示，HCL 与 HCLv 之间最大的差异在于肌肉相关基因 MYF6，其 2 个探针在 HCL 中的表达分别高出 HCLv 18.5 倍和 10.8 倍（p<0.0001）。通过实时定量 PCR（RQ-PCR），152 例经典 HCL 样本中有 100%为 MYF6 阳性，而 90 例献血者中有 5 例（6%）为阳性。在 18 例（35%）HCLv 中也检测到 MYF6 的表达，在 11 例（92%）未突变 IGHV4-34 的 HCL 中，在 35 例（73%）慢性淋巴细胞白血病（CLL）和 12 例（8%）套细胞淋巴瘤中也检测到 MYF6 的表达。MYF6 的低甲基化状态支持 HCL 中比 HCLv 中更多的表达。通过流式细胞术检测到治疗后血液样本呈阴性的 87 例 HCL 患者中有 42 例（48%）仍通过 RQ-PCR 呈 MYF6+，并且 MYF6 RQ-PCR 可以在 105 个正常细胞中检测到 1 个 HCL。MYF6 在 HCL 和大多数 CLL 样本中普遍表达，可能是这些白血病的有用生物标志物。进一步的研究正在进行中，以确定 MYF6 在 HCL 中的作用。
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