RAS mutation in acute myeloid leukemia is associated with distinct cytogenetic subgroups but does not influence outcome in patients younger than 60 years
RAS mutation in acute myeloid leukemia is associated with distinct cytogenetic subgroups but does not influence outcome in patients younger than 60 years
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DOI：
10.1182/blood-2005-03-0867
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发表时间：
2005-09-15
期刊：
影响因子：
20.3
通讯作者：
Linch, DC
中科院分区：
文献类型：
--
作者：
Bowen, DT;Frew, ME;Linch, DC
急性髓系白血病(AML)的发病机制涉及促进增殖/存活的突变和阻碍分化的突变的协同作用。RAS通路被认为是AML增殖驱动的关键组成部分。我们使用变性高效液相色谱或限制性片段长度多态性(RFLP)分析，对主要年龄在60岁以下、在2个临床试验内接受治疗的AML患者进行了NRAS(n=1106)、KRAS(n=739)和HRAS(n=200)热点突变的筛查。NRAS基因突变发生率为11%(126/1106)，KRAS基因突变发生率为5%(39/739)。在随机抽取的200例样本中未检测到HRAS突变。突变频率最高的密码子是N12(43%)、N13(21%)和K12(21%)。KRAS突变在法美英(FAB)M4型中相对过高(P
The pathogenesis of acute myeloid leukemia (AML) involves the cooperation of mutations promoting proliferation/survival and those impairing differentiation. The RAS pathway has been implicated as a key component of the proliferative drive in AML. We have screened AML patients, predominantly younger than 60 years and treated within 2 clinical trials, for NRAS (n = 1106), KRAS (n = 739), and HRAS (n = 200) hot-spot mutations using denaturing high-performance liquid chromatography or restriction fragment length polymorphism (RFLP) analysis. NRAS mutations were confirmed in 11% of patients (126/1106) and KRAS mutations in 5% (39/739). No HRAS mutations were detected in 200 randomly selected samples. Codons most frequently mutated were N12 (43%), N13 (21%), and K12 (21%). KRAS mutations were relatively overrepresented in French-American-British (FAB) type M4 (P