Nature：骨癌中发生突变的TET

　　
　　推荐原文出处：

　　Nature doi:10.1038/nature09586

　　Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2

　　Myunggon Ko,Yun Huang,Anna M. Jankowska,Utz J. Pape,Mamta Tahiliani,Hozefa S. Bandukwala,Jungeun An,Edward D. Lamperti,Kian Peng Koh,Rebecca Ganetzky,X. Shirley Liu,L. Aravind,Suneet Agarwal,Jaroslaw P. Maciejewski& Anjana Rao

　　TET2 is a close relative of TET1, an enzyme that converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA1, 2. The gene encoding TET2 resides at chromosome 4q24, in a region showing recurrent microdeletions and copy-neutral loss of heterozygosity (CN-LOH) in patients with diverse myeloid malignancies3. Somatic TET2 mutations are frequently observed in myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), MDS/MPN overlap syndromes including chronic myelomonocytic leukaemia (CMML), acute myeloid leukaemias (AML) and secondary AML (sAML)4, 5, 6, 7, 8, 9, 10, 11, 12. We show here that TET2 mutations associated with myeloid malignancies compromise catalytic activity. Bone marrow samples from patients with TET2 mutations displayed uniformly low levels of 5hmC in genomic DNA compared to bone marrow samples from healthy controls. Moreover, small hairpin RNA (shRNA)-mediated depletion of Tet2 in mouse haematopoietic precursors skewed their differentiation towards monocyte/macrophage lineages in culture. There was no significant difference in DNA methylation between bone marrow samples from patients with high 5hmC versus healthy controls, but samples from patients with low 5hmC showed hypomethylation relative to controls at the majority of differentially methylated CpG sites. Our results demonstrate that Tet2 is important for normal myelopoiesis, and suggest that disruption of TET2 enzymatic activity favours myeloid tumorigenesis. Measurement of 5hmC levels in myeloid malignancies may prove valuable as a diagnostic and prognostic tool, to tailor therapies and assess responses to anticancer drugs.

　　骨癌病人的治疗药物有哪些？骨癌的治疗可以选择：升血调元汤、参芪十一味颗粒、复方环磷酰胺片等药物进行辅助治疗的。

　　详情请致电我们的客服垂询：400-101-6868。如需购买升血调元汤、参芪十一味颗粒、复方环磷酰胺片，可到临近门店。成都2家分店地址分别为：成都市青羊区文武路158号，门店电话：028-86722949;028-86725308。成都市武侯区玉林北街1号附7、8号 玉林品上1层商铺。（一环路九茹村好又多背面）。门店电话：028-85033975

　　肿瘤科药师温馨提醒：如果发生了骨癌，患者一般会发生病理性骨折或变形，很多骨癌都是由于骨折发展而来的，需要引起重视。