Waldenstroms 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。我们以前的研究结果表明，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。然而，我们发现至少50%的WM肿瘤中存在6q22的小间质缺失。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）。我们正在继续慢病毒策略，这可能使我们能够永生WM肿瘤细胞。最后，我们是DCEG项目的合作者，以确定发生在正常和肿瘤细胞中的遗传异常，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。

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. Our previous 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 showed the following: WM tumors usually are diploid or near diploid with few karyotypic abnomalities, and IgH translocations are extremely rare. However, we have found that small interstitial deletions at 6q22 are present in at least 50% of WM tumors. These results suggest that the molecular pathogeneis of WM is more like chronic lymphocytic leukemia (CLL) than multiple myeloma (MM). We are continuing lentiviral strategies that may enable us to immortalize WM tumor cells. Finally, 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.