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

PU.1诱导骨髓瘤细胞生长停滞和凋亡机制的阐明及其在骨髓瘤治疗中的应用

• 批准号: 23591395
• 负责人: OKUNO YUTAKA
• 金额: $ 3.24万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591395/
• 关键词: 多発性骨髄腫; PU.1; 細胞増殖停止; 細胞死; 癌抑制遺伝子; B細胞リンパ腫; M蛋白; 腫瘍抑制因子; ホジキンリンパ腫; p21; TRAIL

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.

我们在经典霍奇金淋巴瘤细胞系L-428和KM-H2中条件性表达PU.1，并确定PU.1诱导这些细胞的生长停滞和凋亡。慢病毒转导的PU.1表达也诱导来自患者的原发性霍奇金淋巴瘤细胞的凋亡。因此，我们的结论是，PU.1是一个有效的肿瘤抑制剂在经典的霍奇金淋巴瘤细胞。我们以前的条件表达PU.1也诱导生长停滞和凋亡的骨髓瘤细胞系，U266和KMS 12 PE。为了测试PU. 1是否是体内成熟B细胞（包括浆细胞）中的肿瘤抑制因子，我们在生殖后中心B细胞和浆细胞中产生了条件性PU. 1敲除小鼠。在18-24月龄时，这些小鼠中的一些显示脾和/或骨髓中的浆细胞增殖。因此，PU.1可能是体内浆细胞中的肿瘤抑制因子。我们还在分析这些老鼠。

项目成果

Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomide.

• DOI: 10.3892/ijo.2012.1545
• 发表时间: 2012-09
• 期刊: International journal of oncology
• 影响因子: 5.2
• 作者: Kawano Y;Fujiwara S;Wada N;Izaki M;Yuki H;Okuno Y;Iyama K;Yamasaki H;Sakai A;Mitsuya H;Hata H
• 通讯作者: Hata H

血液疾患最新の治療2014-2016, 多発性骨髄腫

2014-2016年血液疾病最新治疗方法，多发性骨髓瘤

• 发表时间: 2014
• 作者: 奥野豊;畑裕之
• 通讯作者: 畑裕之

Three cases of aggressive natural killer cell leukemia with a lethal hemorrhagic complication.

三例伴有致命出血并发症的侵袭性自然杀伤细胞白血病。

• 发表时间: 2012
• 期刊: J Clin Exp Hematop
• 影响因子: 1.5
• 作者: Okuno;Y.;Tatetsu;H.;Nosaka;K.;and Mitsuya;H.
• 通讯作者: H.

IRF4 down-regulation may be involved in PU.1-induced growth arrest/apoptosis in myeloma cells

IRF4 下调可能参与 PU.1 诱导的骨髓瘤细胞生长停滞/凋亡

• 发表时间: 2013
• 作者: Niina Ueno ;Shikiko Ueno;Hiro Tatetsu;Hiromichi Yuki ;Hiroyuki Hata;Tadafumi Iino;Hiroaki Niiro;Koichi Akashi;Hiroaki Mitsuya;Yutaka Okuno
• 通讯作者: Yutaka Okuno

みのがしてはならない血液疾患病理からみた44症例

从血液病病理角度看不可忽视的44例

• 发表时间: 2014
• 作者: 菰原義弘;奥野豊;竹屋元裕
• 通讯作者: 竹屋元裕