Roche J, Zeng C, Barón A, Gadgil S, Gemmill R M, Tigaud I, Thomas X, Drabkin H A
CNRS UMR 6187, Université de Poitiers, 40 Av du Recteur Pineau, Poitiers, Cédex, France.
Leukemia. 2004 Jun;18(6):1059-63. doi: 10.1038/sj.leu.2403366.
We previously reported that favorable and poor prognostic chromosomal rearrangements in acute myeloid leukemia (AML) were associated with distinct levels of HOX expression. We have now analyzed HOX expression in 50 independent adult AML patients (median age=62 years), together with FLT3 and FLT3-ligand mRNA levels, and FLT3 mutation determination. By cluster analysis, we could divide AMLs into cases with low, intermediate and high HOX expression. Cases with high expression were uniquely restricted to a subset of AMLs with intermediate cytogenetics (P=0.0174). This subset has significantly higher levels of FLT3 expression and appears to have an increase of FLT3 mutations (44%), while CEBPalpha mutations were infrequent (6%). FLT3 mRNA levels were correlated with the expression of multiple HOX genes, whereas FLT3 mutations were correlated with HOXB3. In some cases, FLT3 was expressed at levels equivalent to GAPDH in the absence of genomic amplification. We propose that high HOX expression may be characteristically associated with a distinct biologic subset of AML. The apparent global upregulation of HOX expression could be due to growth-factor signaling or, alternatively, these patterns may reflect a particular stage of differentiation of the leukemic cells.
我们之前报道过，急性髓系白血病（AML）中预后良好和不良的染色体重排与不同水平的HOX表达相关。我们现在分析了50例独立的成年AML患者（中位年龄 = 62岁）的HOX表达，同时检测了FLT3和FLT3配体的mRNA水平，并确定了FLT3突变情况。通过聚类分析，我们可将AML分为HOX低表达、中等表达和高表达的病例。高表达病例仅局限于细胞遗传学中等的AML亚组（P = 0.0174）。该亚组的FLT3表达水平显著更高，且似乎FLT3突变增加（44%），而CEBPα突变较少见（6%）。FLT3 mRNA水平与多个HOX基因的表达相关，而FLT3突变与HOXB3相关。在某些情况下，在无基因组扩增时，FLT3的表达水平与甘油醛 - 3 - 磷酸脱氢酶（GAPDH）相当。我们提出，HOX高表达可能特征性地与AML的一个独特生物学亚组相关。HOX表达的明显整体上调可能是由于生长因子信号传导，或者，这些模式可能反映了白血病细胞分化的特定阶段。
