Nf1 and Gmcsf interact in myeloid leukemogenesis
Nf1 and Gmcsf interact in myeloid leukemogenesis
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DOI：
10.1016/s1097-2765(00)80415-3
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发表时间：
2000-01-01
期刊：
影响因子：
16
通讯作者：
Shannon, KM
中科院分区：
文献类型：
--
作者：
Birnbaum, RA;O'Marcaigh, A;Shannon, KM
NF 1肿瘤抑制基因编码神经纤维蛋白，一种p21（ras）（Ras）的GTP酶激活蛋白（GAP）。NF 1患儿易患青少年粒单核细胞白血病（JMML）。一些杂合子Nf 1突变小鼠发生类似的骨髓增生性疾病（MPD），过继转移Nf 1缺陷的胎肝细胞始终诱导这种MPD。人JMML和鼠Nf 1缺陷细胞对甲基纤维素培养物中的粒细胞-巨噬细胞集落刺激因子（GM-CSF）超敏。我们产生了Nf 1和Gmcsf都缺乏的造血细胞，以测试是否需要GM-CSF来驱动体内Nf 1（-/-）细胞的过度增殖。在这里，我们表明，GM-CSF在建立和维持MPD中起着核心作用，并且植入Nf 1（-/-）Gmcsf（-/-）造血细胞的受体对外源性GM-CSF过敏。
The NF1 tumor suppressor gene encodes neurofibromin, a GTPase-activating protein (GAP) for p21(ras) (Ras). Children with NF1 are predisposed to juvenile myelomonocytic leukemia (JMML). Some heterozygous Nf1 mutant mice develop a similar myeloproliferative disorder (MPD), and adoptive transfer of Nf1-deficient fetal liver cells consistently induces this MPD. Human JMML and murine Nf1-deficient cells are hypersensitive to granulocyte-macrophage colony-stimulating factor (GM-CSF) in methylcellulose cultures. We generated hematopoietic cells deficient in both Nf1 and Gmcsf to test whether GM-CSF is required to drive excessive proliferation of Nf1(-/-) cells in vivo. Here we show that GM-CSF plays a central role in establishing and maintaining the MPD and that recipients engrafted with Nf1(-/-) Gmcsf(-/-) hematopoietic cells are hypersensitive to exogenous GM-CSF.