红细胞生成素受体的错义突变在人类红细胞恶性肿瘤是一种罕见的事件。
文章的细节
-
引用
复制到剪贴板 -
Le Couedic JP Mitjavila MT, Villeval杰,Feger F, Gobert年代,麦克斯P, N卡萨德沃尔,Vainchenker W
红细胞生成素受体的错义突变在人类红细胞恶性肿瘤是一种罕见的事件。
血。1996年2月15日,87(4):1502 - 11所示。
- PubMed ID
-
8608241 (在PubMed]
- 文摘
-
人类红细胞恶性肿瘤(真性红细胞增多症(PV)和红白血病)与红细胞生成素(Epo)独立生长和分化。错义或无意义突变促红细胞生成素受体(Epo-R)最近所描述的实验红白血病小鼠和人类在红细胞增多的情况下。寻找一必威国际app个类似的遗传改变在红白血病和PV,我们完全Epo-R基因的外显子测序以及intron-exon连接使用聚合酶链反应在这些障碍。10例1的红白血病,一个等位基因突变被发现在八Epo-R基因外显子改变了天冬酰胺487丝氨酸。没有Epo-r基因突变被发现在12个PV案例研究,但同样的突变(N487S) 1红血球增多症患者中发现不满足标准的PV(来历不明的红血球增多症)。我们没有发现这种突变后的第8外显子测序的一部分Epo-R基因来自21个其他来历不明的红血球增多症患者和51正常对照组。Epo-R突变巴尔virus-derived细胞系中还发现这两种情况下,这表明它不相关的恶性克隆。因此,该突变体没有出现,虽然没有家族病例被发现。这种突变的生物效应,随后进行了研究。红细胞的祖细胞红细胞增多的病人通常对Epo(促红细胞生成素)而从erythroleukemic病人Epo-independent由于自分泌促红细胞生成素刺激。 The normal and the mutated Epo-R were transfected into the murine Ba/F3 cell line. Both types of cells displayed the same response to Epo for proliferation, differentiation, and inhibition of apoptosis. Although this mutation may destroy a consensus binding site for Grb2, no obvious differences either in the pattern of Epo-induced tyrosine phosphorylated proteins or in the binding of Grb2 to the Epo-R were observed. In conclusion, a somatic Epo-R missense mutation does not appear to be a molecular mechanism involved in the abnormal growth of human erythroleukemia and PV. However, the Epo-R mutation (N487S) that we describe is located in the same tyrosine sequence beginning at AA 485 as the one previously observed (P488S) in as case of polycythemia (Sokol et al, Exp Hematol 22:447, 1994). These results suggest that this phosphopeptide sequence may play an important role in Epo signalling.