WALDENSTROM'S MACROGLOBULINEMIA

华氏大球蛋白血症（WM）是一种相对罕见的生发后中心淋巴浆细胞性肿瘤，分泌大量IgM。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。我们开展了以下研究：首先，我们获得了唯一推测的WM细胞系（WSU-WM），并对其进行了分子核型分析；失调c-myc的t（8;14）易位的分子特征测定表达mu和c-myc的突变；并对该细胞系表达的基因进行淋巴芯片微阵列分析。其次，我们已经开发了纯化和表征WM肿瘤细胞的技术，主要重点是使用FISH检测特定染色体的非整倍性以及涉及IgH和IgL位点的易位。初步结果表明，在WM中，IgH开关重组和IgH易位是罕见的，再加上多变性淋巴浆细胞形态表明，IgH开关和浆细胞分化的阻断可能是WM发病的原因之一。第三，我们正在开发能够使WM肿瘤细胞永生的策略。第四，我们是加入WM患者的治疗方案的合作者。最后，我们也是MGUS的化学预防方案的合作者，包括IgM MGUS，它可以代表WM的癌前阶段。我们还将分析上述核型异常的MGUS样本，当这个方案开始时，希望在2001年初。

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. 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. Preliminary 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. Third, we are developing strategies that may enable us to immortalize WM tumor cells. Fourth, we are collaborators in a treatment protocol to which patients with WM have been added. Finally, we are also collaborators in a 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, hopefully early in 2001.