Blood雜志刊登最新研究論文，瑞典哥德堡大學(xué)的研究人員在經(jīng)過(guò)基因修飾的老鼠身上發(fā)現(xiàn),，有兩個(gè)基因,，它們的協(xié)同變異能夠?qū)е虑忠u性白血病的發(fā)生。這項(xiàng)發(fā)現(xiàn)讓科學(xué)家很興奮,，或能有助于新療法的開(kāi)發(fā),。
這兩個(gè)基因在急性白血病患者中通常以變異的形式出現(xiàn)，但是很少出現(xiàn)同時(shí)變異,?？茖W(xué)家之前認(rèn)為這兩個(gè)變異的基因有相同的功能，每個(gè)基因都能單獨(dú)導(dǎo)致一種致癌蛋白R(shí)AS活性增強(qiáng),。這種蛋白轉(zhuǎn)而使得血細(xì)胞迅速擴(kuò)增,。
這項(xiàng)令人驚奇的發(fā)現(xiàn)表明，在癌癥發(fā)展的背后還存在一種未被識(shí)別的機(jī)制,。該研究開(kāi)辟了一條新的對(duì)抗NF1變異的血癌細(xì)胞的通道,。這項(xiàng)研究的負(fù)責(zé)人Martin Bergo教授說(shuō)。
其中的一個(gè)基因能編碼RAS蛋白，在一些癌癥中,，該蛋白是細(xì)胞增殖的加速器,。另一個(gè)基因編碼一種叫NF1的蛋白，該蛋白能降低RAS蛋白的活性,。
研究小組之前使用兩種不同的老鼠模型,，一種是RAS變異的，另一種是NF1變異的,，兩種變異單獨(dú)發(fā)生的老鼠,，其白血病發(fā)展緩慢。然而兩種變異結(jié)合的老鼠則表現(xiàn)出急性白血病的發(fā)展模式,。
研究人員表示,，NF1蛋白可能在白血病發(fā)展的過(guò)程中還承擔(dān)了另外一個(gè)不同的角色，可能根本不涉及RAS蛋白,。這項(xiàng)發(fā)現(xiàn)為開(kāi)發(fā)對(duì)抗白血病的新療法提供了可能,。（生物谷Bioon.com）
生物谷推薦原始出處：
Blood, 22 October 2009, Vol. 114, No. 17, pp. 3629-3632.
Nf1 deficiency co-operates with oncogenic K-RAS to induce acute myeloid leukemia in mice
Briony A. Cutts, Anna-Karin M. Sjogren, Karin M.E. Andersson, Annika M. Wahlstrom, Christin Karlsson, Birgitta Swolin, and Martin O. Bergo*
Wallenberg Laboratory, Institute of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
Institute of Biomedicine, Sahlgrenska University Hospital, Gothenburg, Sweden
Hyperactive RAS signaling is caused by mutations in RAS genes or a deficiency of the neurofibromatosis gene (NF1) and is common in myeloid malignancies. In mice, expression of oncogenic K-RAS or inactivation of Nf1 in hematopoietic cells results in myeloproliferative disorders (MPD) that don't progress to acute myeloid leukemia (AML). Because NF1 is a RAS-GTPase activating protein it has been proposed that NF1 deficiency is functionally equivalent to an oncogenic RAS. It is not clear, however, if Nf1 deficiency would be redundant in K-RAS-induced MPD development or if the two mutations would cooperate in leukemogenesis. Here, we show that the simultaneous inactivation of Nf1 and expression of K-RASG12D in mouse hematopoietic cells results in AML that was fatal in primary mice within four weeks and transplantable to sublethally irradiated secondary recipients. The data point to a strong cooperation between Nf1 deficiency and oncogenic K-RAS.
