Stephenson J, Lizhen H, Mufti G J
Department of Haematological Medicine, Kings College School of Medicine and Dentistry, London, UK.
Leuk Res. 1995 Oct;19(10):741-8. doi: 10.1016/0145-2126(95)00056-t.
The frequency of RAS activation was studied in 48 patients with acute myeloid leukaemia (AML) or with myelodysplastic syndromes (MDS), in order to address the question of whether patients possessing monosomy 7 or other alterations of chromosome 7 have a higher incidence of RAS activation than those lacking chromosome 7 abnormalities. Samples were screened for oncogenic point mutation by DNA amplification followed by oligonucleotide hybridization analysis at codons 12, 13 and 61 of N-RAS and codons 12 and 13 of K-RAS. Two additional samples were considered to have activated RAS due to additional karyotypic abnormalities t(5;12) or loss of both copies of chromosome 17 and hence, the neurofibromatosis (NF1) loci. The group of chronic myelomonocytic leukaemia (CMML) patients had activated RAS in 4/11 cases and inclusion of two CMMLt patients (with monosomy 7) brings this incidence to 5/13. No change in frequency of RAS activation was seen between groups containing de novo AML samples with or without chromosome 7 abnormalities (1/5 and 2/12, respectively). However, assessment of MDS samples in the process of, or subsequent to, leukaemic progression showed a difference between the two groups. The frequency of RAS activation in samples with monosomy 7 was 4/9 samples while none of the seven samples without chromosome 7 changes showed RAS activation. The co-existence of RAS activation and monosomy 7 in MDS indicates that these lesions can co-operate in the multistep process of leukemogenesis.
对48例急性髓系白血病（AML）或骨髓增生异常综合征（MDS）患者的RAS激活频率进行了研究，以探讨具有7号染色体单体或7号染色体其他改变的患者RAS激活发生率是否高于无7号染色体异常的患者。通过DNA扩增，随后对N-RAS的第12、13和61密码子以及K-RAS的第12和13密码子进行寡核苷酸杂交分析，对样本进行致癌点突变筛查。另外两个样本因额外的核型异常t(5;12)或17号染色体两个拷贝均缺失以及神经纤维瘤病（NF1）基因座而被认为RAS激活。慢性粒单核细胞白血病（CMML）患者组中有4/11例RAS激活，纳入两名CMMLt患者（有7号染色体单体）后，这一发生率变为5/13。在含有或不含有7号染色体异常的初发AML样本组之间，RAS激活频率未见变化（分别为1/5和2/12）。然而，对白血病进展过程中或之后的MDS样本评估显示两组之间存在差异。有7号染色体单体的样本中RAS激活频率为4/9，而7个无7号染色体改变的样本均未显示RAS激活。MDS中RAS激活与7号染色体单体并存表明这些病变可在白血病发生的多步骤过程中协同作用。
