造血系谱切换:v-raf瘤基因将Emu-myc转基因B细胞转化为巨细胞
S P Klinken1, W S Alexander, J M Adams
1Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Cell
|June 17, 1988
概括
构成性表达c-myc和v-raf瘤基因可以破坏正常细胞发育. 淋巴细胞可以被重新编程成髓状细胞,这表明某些癌症的潜在机制.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 细胞分化是一个严格规范的过程.
- 像c-myc和v-raf这样的瘤基因在细胞生长和增殖中起着至关重要的作用.
- 血液构造系承诺的违反可以导致血液瘤.
研究的目的:
- 为了研究同时c-myc和v-raf瘤基因表达对B系细胞分化的影响.
- 为了确定淋巴细胞是否可以被重新编程成其他细胞系.
主要方法:
- 感染B系细胞 (来自Emu-myc转基因小鼠的淋巴瘤和白血病前骨髓) 与v-raf携带的逆转录病毒.
- 细胞分化成巨细胞的评估,使用形态学,粘附性,细胞活性,表面标记物和酶生产.
- 免疫球蛋白基因重排的分析,转基因表达,瘤性,GM-CSF的产生,以及型变化.
主要成果:
- B血统细胞经常切换到髓状血统,成为巨细胞.
- 转换细胞保留了克隆类型的免疫球蛋白基因重排,但显示了减少的Emu-myc转基因表达.
- 不同化的细胞仍然具有瘤性,并产生了粒细胞-巨细胞殖民地刺激因子 (GM-CSF).
- 大多数转换细胞系都表现出型变异.
结论:
- 同时表达的myc和raf瘤基因可以克服正常的血液系系的承诺.
- 淋巴细胞在致癌性压力下可以经历基因重编程,变成髓状细胞.
- 这种重编程可能有助于骨髓质恶性瘤的发展.
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