Carnicer Maria J, Nomdedéu Josep F, Lasa Adriana, Estivill Camino, Brunet Salut, Aventín Anna, Sierra Jorge
Laboratori d'Hematologia, Hospital de la Santa Creu i Sant Pau, Avda Sant Antoni M Claret, 167, 08025 Barcelona, Spain.
Leuk Res. 2004 Jan;28(1):19-23. doi: 10.1016/s0145-2126(03)00125-5.
The basic molecular defects underlying acute myeloid leukemias (AML) seem to be caused by inactivating mutations in transcription factors which control normal myeloid differentiation (Class II mutations) and genetic lesions in tyrosine kinases resulting in constitutive activation (Class I mutations). We sought to determine the frequency of associated mutations (Class I + Class II) in a consecutive series of adult de novo AML (353 patients) in order to stress the validity of this model. Mutations and rearrangements at the FLT3, AML1/ETO, CBFbeta/MYH11, AML1, CEBPalpha and MLL genes were investigated using standard molecular methods. Despite the limitations of the study (DNA availability hampered c-kit and ras mutational analysis), 3.4% of patients showed Class I + Class II mutations. Our findings could be consistent with the cooperative model. The search for new tyrosine kinases which can be the target of molecular lesions in AML warrants further investigation.
急性髓系白血病（AML）潜在的基本分子缺陷似乎是由控制正常髓系分化的转录因子失活突变（II类突变）以及酪氨酸激酶中的遗传损伤导致的组成性激活（I类突变）引起的。我们试图确定连续一系列成人初发AML（353例患者）中相关突变（I类 + II类）的频率，以强调该模型的有效性。使用标准分子方法研究了FLT3、AML1/ETO、CBFβ/MYH11、AML1、CEBPα和MLL基因的突变和重排。尽管该研究存在局限性（DNA可用性阻碍了c-kit和ras突变分析），但3.4%的患者显示出I类 + II类突变。我们的发现可能与协同模型一致。寻找可成为AML分子损伤靶点的新酪氨酸激酶值得进一步研究。
