Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells
Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells
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DOI：
10.1182/blood.v99.5.1745
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发表时间：
2002-03-01
期刊：
影响因子：
20.3
通讯作者：
Shaughnessy, J
中科院分区：
文献类型：
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作者：
Zhan, FH;Hardin, J;Shaughnessy, J
用CD 138（+）选择法纯化74例初诊多发性骨髓瘤（MM）、5例意义不明单克隆丙种球蛋白病（MGUS）和31例健康志愿者（正常PC）的骨髓血浆细胞（PC）。纯化的PC和7 MM细胞系的基因表达谱使用高密度寡核苷酸微阵列询问约6800个基因。在系统聚类分析中，正常和MM PC被区分，并确定了4个不同的MM亚组（MM 1，MM 2，MM 3和MM 4）。MM 1的表达模式与正常PC和MGUS相似，而MM 4与MM细胞系相似。与不良预后、异常核型（P =.002）和高血清β（2）-微球蛋白水平（P =.0005）相关的临床参数在MM 4中最常见。此外，在MM 1和MM 4的比较中，参与DNA代谢和细胞周期控制的基因过表达。此外，通过X-2和Wilcoxon秩和检验，鉴定了120个新的候选疾病基因，这些基因可区分正常和恶性PC（P
Bone marrow plasma calls (PCs) from 74 patients with newly diagnosed multiple myeloma (MM), 5 with monoclonal gammopathy of undetermined significance (MGUS), and 31 healthy volunteers (normal PCs) were purified by CD138(+) selection. Gene expression of purified PCs and 7 MM cell lines were profiled using high-density oligonucleotide microarrays interrogating about 6800 genes. On hierarchical clustering analysis, normal and MM PCs were differentiated and 4 distinct subgroups of MM (MM1, MM2, MM3, and MM4) were Identified. The expression pattern of MM1 was similar to normal PCs and MGUS, whereas MM4 was similar to MM cell lines. Clinical parameters linked to poor prognosis, abnormal karyotype (P =.002) and high serum beta(2)-microglobulin levels (P =.0005), were most prevalent in MM4. Also, genes involved in DNA metabolism and cell cycle control were overexpressed in a comparison of MM1 and MM4. In addition, using X-2 and Wilcoxon rank sum tests, 120 novel candidate disease genes were identified that discriminate normal and malignant PCs (P