The elucidation of the mechanisms of growth arrest and apoptosis in myeloma cells induced by PU.1 and its utility for myeloma treatment

我们在经典霍奇金淋巴瘤细胞系L-428和KM-H2中有条件地表达了PU1，并鉴定了PU1诱导了这些细胞的生长停滞和凋亡。慢病毒转导的PU.1表达也可诱导患者原代霍奇金淋巴瘤细胞发生凋亡。因此，我们得出结论，PU1在经典霍奇金淋巴瘤细胞中是一种有效的肿瘤抑制因子。我们先前条件表达的PU1还可以诱导骨髓瘤细胞系U266和KMS12PE的生长停滞和凋亡。为了在体内测试PU.1在包括浆细胞在内的成熟B细胞中是否具有肿瘤抑制作用，我们在生发中心后B细胞和浆细胞中建立了条件基因敲除小鼠。在18-24个月龄时，部分小鼠的脾和/或骨髓出现浆细胞增殖。因此，PU1可能是体内浆细胞中的一种肿瘤抑制因子。我们仍在分析这些老鼠。

We conditionally expressed PU.1 in classical Hodgkin lymphoma cell lines, L-428 and KM-H2, and identified that PU.1 induced growth arrest and apoptosis in these cells. Lentiviral transduced PU.1 expression also induced apoptosis in primary Hodgkin lymphoma cells from patients. Therefore, we concluded that PU.1 is a potent tumor suppressor in classical Hodgkin lymphoma cells.We previously conditional expressed PU.1 also induces growth arrest and apoptosis in myeloma cell lines, U266 and KMS12PE. To test whether PU.1 is a tumor suppressor in mature B cells, including plasma cells, in vivo, we generated conditional PU.1 knockout mice in post germinal center B cells and plasma cells. At the age of 18-24 months, some of these mice shows a proliferation plasma cells in spleen and/or bone marrow. Therefore, PU.1 might be a tumor suppressor in plasma cells in vivo. We are still analyzing these mice.