Waldenstrom's Macroglobulinemia

瓦尔登斯特伦巨球蛋白血症是一种分泌大量IgM的相对罕见的生殖中心淋巴浆细胞肿瘤。虽然WM与淋巴浆细胞性淋巴瘤和多发性骨髓瘤有一些相似之处，但对WM的分子发病机制知之甚少。我们已开始进行以下研究。首先，我们已经获得了唯一假定的WM细胞系（WSU-WM），并进行了研究：分子核型分析; t（8;14）易位，失调c-myc的分子特征;突变的确定在表达亩和c-myc;和淋巴芯片芯片分析在这条线上表达的基因。不幸的是，不可能获得原发性肿瘤样品来证明该细胞系来源于WM肿瘤，因此该细胞系的结果可能与WM肿瘤无关。第二，我们已经开发了纯化和表征WM肿瘤细胞的技术，主要集中在使用FISH检测特定染色体的非整倍体加上涉及IgH和IgL位点的易位。我们的研究结果表明，免疫球蛋白H开关重组和免疫球蛋白H易位是罕见的WM，这与多嗜性淋巴浆细胞形态表明，阻断免疫球蛋白H开关和浆细胞分化可能有助于这种肿瘤的发病机制。此外，我们与R. Fonseca在马约诊所的研究表明：WM肿瘤通常是二倍体或近二倍体，核型异常很少，IgH易位非常罕见。这些结果提示，WM的分子发病机制更像慢性淋巴细胞白血病（CLL）而非多发性骨髓瘤（MM）。第三，我们正在开发可能使我们能够使WM肿瘤细胞永生化的策略。第四，我们是DCEG项目的合作者，该项目旨在鉴定正常细胞和肿瘤细胞中发生的遗传异常，这些细胞来自于具有两个或多个WM或IgM MGUS个体的家庭成员。最后，我们也是一个多机构的MGUS化学预防方案的合作者，包括IgM MGUS，可以代表WM的癌前阶段。当本方案开始时，我们还将分析MGUS样本的核型异常，如上所述。

Waldenstrom's macroglobulinemia (WM) is a relatively rare post-germinal center lymphoplasmacytic tumor that secretes large amounts of IgM. Although WM has some similarities to lymphoplasmacytic lymphoma and multiple myeloma, very little is known about the molecular pathogenesis of WM. We have initiated the following studies. First, we have obtained the only putative WM cell line (WSU-WM) and have studied it by: molecular karyotypic analyses; molecular characterization of a t(8;14) translocation that dysregulates c-myc; determination of mutations in expressed mu and c-myc; and lymphochip microarray analysis of genes expressed in this line. Unfortunately, it has been impossible to obtain a primary tumor sample to prove that this line is derived from a WM tumor, so that the results on this cell line may not relate to WM tumors. Second, we have developed the technology to purify and characterize WM tumor cells, with a major focus of using FISH to detect aneuploidy of specific chromosomes plus translocations involving IgH and IgL loci. Our results indicate that IgH switch recombination and IgH translocations are rare in WM, which together with the pleotropic lymphoplasmacytic morphology suggest that a block to IgH switching and plasma cell differentiation may contribute to the pathogenesis of this tumor. In addition, our collaborative results with R. Fonseca at the Mayo Clinic show the following: WM tumors usually are diploid or near diploid with few karyotypic abnomalities, and IgH transloctions are extremely rare. These results suggest that the molecular pathogeneis of WM is more like chronic lymphocytic leukemia (CLL) than multiple myeloma (MM). Third, we are developing strategies that may enable us to immortalize WM tumor cells. Fourth, we are collaborators in a DCEG project to identify genetic abnormalities that occur in normal and tumor cells derived from individuals who are are members of families that have two or more individuals with WM or IgM MGUS. Finally, we are also collaborators in a multi-institutional chemoprevention protocol for MGUS, including IgM MGUS that can represent a premalignant stage of WM. We will also be analyzing the MGUS samples for karyotypic abnormalities as described above when this protocol begins.