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多发性骨髓瘤(MM)是异常浆细胞大量克隆增殖的恶性肿瘤,约占血液系统肿瘤的10%,在临床表现、遗传学改变、预后等方面存在很大异质性。随着疾病进展会出现继发性染色体改变,如myc重排、del(13q)、del(17p)、del(1p)、amp(1q),本综述将针对MM常见的细胞分子遗传异常进行总结。一、1号染色体(1q)异常1.1q结构简介:MM中1q畸变最初在传统细胞遗传学中被发现,包括1q12~q23正向和反向重复、1q等臂染色体、1q跳跃性易位[1-2],1q尤其1q12~q23这一段区域包含大量与骨髓瘤相关的候选基因,如PSMD4、PDZK1、IL6R、BCL9、CKS1B,我们重点讨论1q21区域的基因。MM中IL-6受体数目基因量效性增加,进而激活与肿瘤生长增殖相关的信号通路,包括JAK/STAT-3、MEK/ERK和PI3-K[3],可加强破骨细胞的溶骨效应[4-5],促进骨髓中浆细胞增殖,进而分泌大量的β2微球蛋白(β2-MG),预后差,生存期短。另外,CKS1B基因也定位于1q21区域,属于Cks/Sucl蛋白家族,是通过SKP2-p27依赖性和非依赖性途径影响骨髓瘤细胞增殖和生存[6-7]。在骨髓瘤细胞中,CKS1B基因敲除引起SKP2表达降低和p27表达上调,并且导致强烈的细胞凋亡和生长抑制。进一步研究证实,STAT3、MEK/ERK、BCL2是CKS1B的下游调控
Multiple myeloma (MM) is a malignant tumor with a large number of abnormal plasma cells clonal proliferation, accounting for about 10% of hematological malignancies. There is a great heterogeneity in clinical manifestations, genetics and prognosis. Secondary chromosomal changes occur as the disease progresses, such as myc rearrangement, del (13q), del (17p), del (1p), and amp (1q). This review summarizes common cell molecular genetic abnormalities in MM . First, chromosome 1 (1q) abnormal 1.1q Structure Description: 1q aberrations in MM initially found in traditional cytogenetics, including 1q12 ~ q23 forward and reverse repeats, 1q and other arm chromosomes, 1q jumping translocation [ 1-2], 1q especially 1q12 ~ q23 this region contains a large number of myeloma related candidate genes, such as PSMD4, PDZK1, IL6R, BCL9, CKS1B, we focus on the 1q21 region of the gene. The increased number of IL-6 receptor genes in MM leads to the activation of signaling pathways associated with tumor growth and proliferation, including JAK / STAT-3, MEK / ERK and PI3-K [3] Bone effect [4-5], promote the proliferation of bone marrow plasma cells, thereby secrete a large amount of β2 microglobulin (β2-MG), the prognosis is poor, short survival. In addition, the CKS1B gene is also located in the 1q21 region, which belongs to the Cks / Sucl protein family and affects the proliferation and survival of myeloma cells through SKP2-p27-dependent and independent pathways [6-7]. In myeloma cells, CKS1B knockdown causes a decrease in SKP2 expression and an up-regulation of p27 expression, and leads to strong apoptosis and growth inhibition. Further studies confirmed that STAT3, MEK / ERK, BCL2 is CKS1B downstream regulation