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Studies on the mechanism by which leukemic blast progenitors grow indefinitely.

研究白血病细胞祖细胞无限生长的机制。

基本信息

批准号：
62570538
负责人：
NARA Nobuo
金额：
$ 1.15万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570538/
关键词：
Acute myeloblastic leukemia Leukemic blast progenitor Self-renewal Growth factor Receptor サイトカイン G-CSF GM-CSF M-CSF IL-1 顆粒球系コロニー刺激因子 IL-3

项目摘要

The purpose of this study is to analyse the mechanism by which leukemic cells grow indefinitely in acute myeloblastic leukemia (AML) patients. AML is a clonal hemopathy with the progressive accumulation of leukemic blasts and the decreased normal hemopoiesis. The accumulation of blasts is maintained by only a small subpopulation, leukemic blast progenitors. Leukemic blast progenitors may renew themselves and/or undergo terminal divisions with limited differentiation. The growth and differentiation of blast progenitors were studied in methylcellulose and suspension cultures in the present study. The results show that normal granulopoietic growth factor such as G-CSF, GM-CSF, M-CSF, and IL-3 stimulate the growth of blast progenitors. The receptors for GM-CSF and IL-1 were noted on blasts.In term of therapy for AML, the self-remewal activity of blast progenitors should be eliminated completely because the self-renewal capacity is highly correlated with clinical outcome. In the present study we confirmed that cytosine arabinoside, interferon, tumor necrosis factor and transforming growth factor were effective against the self-renewal of blast progenitors.In the future work, we would like to determine the mechanism of leukemic cells growth more precisely and develope more efficient therapy for AML.

本研究的目的是分析白血病细胞在急性髓细胞白血病（AML）患者中无限生长的机制。急性髓细胞白血病（AML）是一种以白血病原始细胞进行性聚集和正常造血功能下降为特征的克隆性血液病。原始细胞的积累仅由一小部分亚群白血病原始细胞祖细胞维持。白血病母细胞祖细胞可以自我更新和/或进行有限分化的终末分裂。本研究采用甲基纤维素和悬浮培养两种方法，研究了胚祖细胞的生长和分化。结果表明，正常的粒细胞生长因子如G-CSF、GM-CSF、M-CSF和IL-3刺激原始祖细胞的生长。在AML的治疗中，应彻底消除原始祖细胞的自我更新能力，因为其自我更新能力与临床预后密切相关。本研究证实了阿糖胞苷、干扰素、肿瘤坏死因子和转化生长因子对白血病细胞的自我更新有抑制作用，希望在今后的工作中能更准确地阐明白血病细胞的生长机制，并开发出更有效的AML治疗方法。