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)過基因修飾的老鼠身上發(fā)現(xiàn),，有兩個基因，它們的協(xié)同變異能夠?qū)е虑忠u性白血病的發(fā)生,。這項發(fā)現(xiàn)讓科學(xué)家很興奮,，或能有助于新療法的開發(fā)。
這兩個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)同時變異,。科學(xué)家之前認為這兩個變異的基因有相同的功能,，每個基因都能單獨導(dǎo)致一種致癌蛋白RAS活性增強,。這種蛋白轉(zhuǎn)而使得血細胞迅速擴增。
這項令人驚奇的發(fā)現(xiàn)表明,，在癌癥發(fā)展的背后還存在一種未被識別的機制,。該研究開辟了一條新的對抗NF1變異的血癌細胞的通道。這項研究的負責人Martin Bergo教授說,。
其中的一個基因能編碼RAS蛋白,，在一些癌癥中，該蛋白是細胞增殖的加速器。另一個基因編碼一種叫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)展的過程中還承擔了另外一個不同的角色,，可能根本不涉及RAS蛋白,。這項發(fā)現(xiàn)為開發(fā)對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.
