HOX expression patterns identify a common signature for favorable AML.
HOX expression patterns identify a common signature for favorable AML.
复制标题
作者：
由染色体易位和髓淋巴细胞白血病（MLL）重排引起的HOX表达失调是某些类型白血病的病因。利用实时逆转录pcr技术，我们检测了119例新诊断的成人急性髓系白血病（AMLs）患者中43个聚集性HOX、polycomb、MLL和FLT3基因的表达。HOX表达下调是有利AMLs的一致特征，在这些病例中，有16例具有不同的表达谱。在另外44个样本中使用17个基因预测器，我们观察到区分有利与中间/不利细胞遗传学组的特异性为94.7%。在其他AMLs中，HOX过表达与核磷蛋白（NPM）突变有关，我们还发现了一个与wt-NPM表型相似的亚群。在许多不利的和其他中间细胞遗传学AMLs中，HOX水平与正常CD34+细胞相似，除了正常样本的均匀性特征不存在。我们还观察到HOXA9水平与生存率呈显著负相关，并且11q23重排病例中BMI-1过表达，提示p19ARF抑制可能参与mll相关白血病。这些结果强调了HOX表达模式与某些形式的AML之间的密切关系，并强调需要确定这些差异是否在疾病过程中发挥作用。
Deregulated HOX expression, by chromosomal translocations and myeloid-lymphoid leukemia (MLL) rearrangements, is causal in some types of leukemia. Using real-time reverse transcription-PCR, we examined the expression of 43 clustered HOX, polycomb, MLL and FLT3 genes in 119 newly diagnosed adult acute myeloid leukemias (AMLs) selected from all major cytogenetic groups. Downregulated HOX expression was a consistent feature of favorable AMLs and, among these cases, inv(16) cases had a distinct expression profile. Using a 17-gene predictor in 44 additional samples, we observed a 94.7% specificity for classifying favorable vs intermediate/unfavorable cytogenetic groups. Among other AMLs, HOX overexpression was associated with nucleophosmin (NPM) mutations and we also identified a phenotypically similar subset with wt-NPM. In many unfavorable and other intermediate cytogenetic AMLs, HOX levels resembled those in normal CD34+ cells, except that the homogeneity characteristic of normal samples was not present. We also observed that HOXA9 levels were significantly inversely correlated with survival and that BMI-1 was over-expressed in cases with 11q23 rearrangements, suggesting that p19ARF suppression may be involved in MLL-associated leukemia. These results underscore the close relationship between HOX expression patterns and certain forms of AML and emphasize the need to determine whether these differences play a role in the disease process.
登录
查看更多内容
影响因子：
158.5
作者：
Falini, B;Mecucci, C;Martelli, MF
通讯作者：
Martelli, MF
影响因子：
56.9
作者：
Golub, TR;Slonim, DK;Lander, ES
通讯作者：
Lander, ES
影响因子：
2.6
作者：
Antonchuk, J;Sauvageau, G;Humphries, RK
通讯作者：
Humphries, RK
影响因子：
20.3
作者：
Crooks, GM;Fuller, J;Gasson, JC
通讯作者：
Gasson, JC
影响因子：
3.7
作者：
Debernardi, S;Lillington, DM;Young, BD
通讯作者：
Young, BD