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GM-CSF、IL-3和IL-5受体βC链中的激活点突变并非急性髓系白血病发病机制中的主要促成因素。

Activating point mutations in the betaC chain of the GM-CSF, IL-3 and IL-5 receptors are not a major contributory factor in the pathogenesis of acute myeloid leukaemia.

作者信息

Freeburn R W, Gale R E, Linch D C

机构信息

Department of Haematology, University College London Medical School.

出版信息

Br J Haematol. 1998 Oct;103(1):66-71. doi: 10.1046/j.1365-2141.1998.00939.x.

Abstract

A number of mutant growth factor receptors have been described which are constitutively activated and confer factor independence on growth factor dependent cells, possibly through constitutive dimerization in the absence of ligand or induction of a conformational change. Mutations in receptor chains may therefore contribute to the pathogenesis of haemopoietic malignancies, for example by causing constitutive receptor activation or uncontrolled downstream signalling. Since most of the activated mutants reported for the betaC chain of the GM-CSF/IL-3/IL-5 receptor involve point mutations or truncations of the extracellular domain, we have analysed the coding sequence of this region using RT-PCR-SSCP of RNA from blast cells of 31 patients with acute myeloid leukaemia (AML). Two point mutations detected were silent, C301-->T (Cys91) and C1306-->T (Ser426). The latter had previously been identified with an allele frequency of 0.13 in the general population. Two further point mutations detected led to amino acid substitutions, G773-->C (Glu249Gln), which is equivalent to the mouse sequences, and G962-->A (Asp312Asn), both of which were found at similar frequencies in normal controls. Activating mutations of the betaC chain which might contribute to the pathogenesis of the disease are therefore rare in AML.

摘要

已经描述了许多突变的生长因子受体,它们组成性激活并赋予依赖生长因子的细胞因子非依赖性,这可能是通过在没有配体的情况下组成性二聚化或诱导构象变化实现的。因此,受体链中的突变可能导致造血系统恶性肿瘤的发病机制,例如通过引起受体组成性激活或不受控制的下游信号传导。由于报道的GM-CSF/IL-3/IL-5受体βC链的大多数激活突变体涉及细胞外结构域的点突变或截短,我们使用来自31例急性髓性白血病(AML)患者原始细胞的RNA的RT-PCR-SSCP分析了该区域的编码序列。检测到的两个点突变是沉默的,C301→T(Cys91)和C1306→T(Ser426)。后者先前在普通人群中的等位基因频率为0.13。检测到的另外两个点突变导致氨基酸取代,G773→C(Glu249Gln),与小鼠序列等同,以及G962→A(Asp312Asn),两者在正常对照中的频率相似。因此,可能导致疾病发病机制的βC链激活突变在AML中很少见。

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