分子遗传学和表观遗传学异常在T淋巴母细胞淋巴瘤/白血病中的预后价值的研究进展

摘要

T lymphoblastic lymphoma / leukemia is a strong invasive and has a high incidence of various molecular genetic abnormalities.The NOTCH1 / FBXW7 mutation is one of the most common mutations,and related with good prognosis in T-LBL / ALL.PTEN mutation,a poor prognostic factor,could be overcome by NOTCH1 mutations in pediatric patients to some extent.Patients with MLL gene abnormality and loss of heterozygosity 6q have worse prognosis than those with normal karyotype.The incidence of MLL gene abnormality,RUNX1 mutation and DNMT3A mutation in early precursor T-lymphoblastic leukemia was higher than that of other mature subtypes,which could be used as risk stratification factors.Epigenetic abnormalities play an important role in the malignant transformation of stem cells.Epigenetics treatment such as demethylation therapy may improve the prognosis of high-risk patients.In this article,the NOTCH1,FBXWT,PTEN and RAS gene mutations and prognosis,the molecular and cellular abnormalities and prognosis, as well as epigenetic abnormality and prognosis are reviewed.%T淋巴母细胞淋巴瘤/白血病(T-LBL/L)侵袭性强和基因突变等分子遗传学异常发生率高.NOTCH1/FBXW7突变是最常见的一种基因突变,在T-LBL/ALL中与良好的预后相关;PTEN突变是不良预后因素,在儿童患者中能够一定程度地被NOTCH1突变克服.发生MLL基因异常和6号染色体杂合性缺失的患者,其预后差于核型正常患者.早期前体T淋巴细胞白血病中MLL基因异常、RUNX1突变和DNMT3A突变发生率高于其他成熟亚型,可以作为危险度分层的指标.表观遗传学异常在造血干细胞的恶性改变中起着重要作用,针对表观遗传学的治疗如去甲基化药物或者能够改善高危患者的预后.本文就NOTCH1/ FBXW7/ PTEN/ RAS基因突变与预后,分子和细胞学异常与预后,以及表观遗传学与预后关系进行综述.