Constitutuve activation of MAPK activity in leukemic cells-its role in cellular proliferration

白血病细胞中MAPK活性的组成型激活-其在细胞增殖中的作用

• 批准号: 10670966
• 负责人: MUROHASHI Ikuo
• 金额: $ 1.79万
• 依托单位: Saitama Prefectural University, Junior College (1999-2000)Saitama Medical University (1998)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670966/
• 关键词: Hematological malignancies; ERK1; ERK2 MAP kinase; Protein kinase C; PI3-kinase; Akt kinase; thalidomide; angiogenic factors; angiogenesis; ERK_1; ERK_2MAPキナーゼ; アポトーシス; protein kinase C; PT3-キナーゼ; ERK_2 MAPキナーゼ; PI3-キナーゼ

ERK1/ERK2 mitogen-activated protein kinase (MAPK) has been shown to play an important role in proliferation, prevention of apoptosis, and differentiation of hematopoietic cells, including malignant cell. We investigated the role and activity of MAPK activity in cells from patients with myeloid and lymphoid malignant neoplasms.1. MAPK activity in myeloid malignanciesWe showed that an appropriate hematopoietic growth factor (HG) differentially prevents apoptosis and stimulates mitosis, and stimulates the growth of leukemic cells from patients with acute myeloblastic leukemia (I Murohashi et al. : Exp Hematol 25 : 1942, 1997). AMPK activity paralleled with growth of AML blast clonogenic cells after stimulation with G-CSF or IL-3 (I Murohashi et al. : Blood 96 : 141b, 2000). AML patients could be divided into three groups by their growth patterns ; growth factor-dependent growth ; autocrine growth ; autonomous growth. Patients with spontaneous colony formation had significantly higher MAPK activity compared with those without spontaneous colony formation. It is postulated that MAPK activity must be associated with their prognosis.2. MAPK activity in lymphoid malignanciesConstitutive MAPK activation was noted in all 100 patients with lymphoid malignancies, where phosphorylation of Akt was observed in 75% of the patients (T Takahashi, I Murohashi et al. : Blood 92 : 376a, 1998). The MAPK activity also seems to be related to their prognosis.3. Conclusions and future studiesMAPK activity has been shown to play an important role in the growth of hematological malignancies. Further studies are required to define its effectors and functions. The role of MAPK in angiogenesis remains to be clarified.

ERK 1/ERK 2丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）在造血细胞（包括恶性肿瘤细胞）的增殖、凋亡和分化中起重要作用。我们研究了髓系和淋巴系恶性肿瘤患者细胞中MAPK活性的作用和活性。我们表明，适当的造血生长因子（HG）有差别地防止细胞凋亡和刺激有丝分裂，并刺激来自急性成髓细胞白血病患者的白血病细胞的生长（I Murohashi等：Exp Hematol 25：1942，1997）。在用G-CSF或IL-3刺激后，AMPK活性随着AML母细胞克隆形成细胞的生长而增加（IMurohashi等：Blood 96：141 b，2000）。根据AML患者的生长方式，可将其分为三组：生长因子依赖性生长、自分泌生长和自主生长。有自发集落形成的患者MAPK活性明显高于无自发集落形成的患者。推测MAPK的活性与它们的增殖有关.淋巴恶性肿瘤中的MAPK活性在所有100名淋巴恶性肿瘤患者中观察到组成性MAPK活化，其中在75%的患者中观察到Akt磷酸化（T Takahashi，I Murohashi等：Blood 92：376 a，1998）。MAPK的活性也可能与它们的增殖有关.结论和未来的研究已证明MAPK活性在血液恶性肿瘤的生长中发挥重要作用。需要进一步的研究来确定其效应器和功能。MAPK在血管生成中的作用仍有待阐明。

项目成果

K Kishimoto et al.: "Molecular events in exponential clonogenic cell growth of The growth factor dependent leukemia cell line, MO7E"J Saitama Med School. 25. 75-84 (1998)

K Kishimoto 等人：“生长因子依赖性白血病细胞系 MO7E 的指数克隆细胞生长中的分子事件”J Saitama Med School。

編集(室橋郁生 他): "血液疾患入門Picture Test"メディカルレビュー社268. 269 (2000)

室桥郁夫等编辑：《血液疾病的图片测试入门》医学评论公司 268. 269 (2000)

I Murohashi, T Takahashi et al.: "Roles of mitogen-activated protein kinase activity in the in vitro growth of blast clonogenic cells from patients with acute myeloblastic leukemia."submitted for publication.

I Murohashi、T Takahashi 等人：“丝裂原激活蛋白激酶活性在急性髓细胞白血病患者的母细胞克隆细胞体外生长中的作用”，已提交出版。

Murohashi I et al.: "Establishment and characterization of a B-cell acute lymphoblastic leukemia Fab type L3 cell line, SPU-1."Bulletin Saitama Prefectural University. (in press). (2000)

Murohashi I 等人：“B 细胞急性淋巴细胞白血病 Fab 型 L3 细胞系 SPU-1 的建立和表征。”埼玉县立大学通报。

T Takahashi, I Murohashi et al.: "Constitutive activation of ERK1/ERK2 mitogen-activated protein kinase in multiple myeloma."J Saitama Medical School. 26. 59-66 (1999)

T Takahashi、I Murohashi 等人：“多发性骨髓瘤中 ERK1/ERK2 丝裂原激活蛋白激酶的组成型激活。”J Saitama Medical School。