Dawczynski Kristin, Steinbach Daniel, Wittig Susann, Pfaffendorf Nadine, Kauf Eberhard, Zintl Felix
Friedrich-Schiller University Jena, Department of Pediatrics, Jena, Germany.
Pediatr Blood Cancer. 2008 Jan;50(1):24-8. doi: 10.1002/pbc.21294.
Insulin-like growth factor (IGF) system as regulator for cellular proliferation is of particular interest in search for new prognostic approaches in cancer treatment.
We analyzed the mRNA expression profile of IGF-I, -II, and IGFBP-2, -3 in 50 children with previously untreated AML (mean age 10.8 +/- 4.8 years; patients in CCR n = 20, patients with relapse during later course of disease n = 15). MNC samples from peripheral blood as well as bone marrow of healthy donors were used as controls.
IGFBP-2 expression was significantly higher in AML cells than in healthy cells of peripheral MNC (P < 0.001) and of bone marrow cells (P < 0.01). Conversely, AML cells showed significantly lower IGFBP-3 and IGF-I gene expression compared to controls (P = 0.02; P < 0.001). Patients with relapse (median +/- range: 0.0929 +/- 0.049) during later course of disease demonstrated higher IGFBP-2 expression compared to patients in CCR (0.0121 +/- 0.047; P = 0.06) at time of diagnosis. A multivariate analysis identified the IGFBP-2 mRNA expression as an independent factor for the prediction of relapse. Furthermore, the probability of relapse-free survival (RFS) in patients with IGFBP-2 mRNA level >0.1000 was 28%; whereas, the probability of RFS in patients with IGFBP-2 mRNA level <0.1000 was 62% (P = 0.04, log-rank test). No prognostic influence could be found for the other investigated genes.
Results identified different expressions of IGF components between normal and AML cells. Patients with IGFBP-2 mRNA levels up to 0.1000 (relative to KG1 cell line) more likely developed a relapse. Identification of these patients at diagnosis may allow more individualized treatment.
胰岛素样生长因子（IGF）系统作为细胞增殖的调节因子，在寻找癌症治疗新的预后方法方面备受关注。
我们分析了50例未经治疗的急性髓系白血病（AML）儿童（平均年龄10.8±4.8岁；完全缓解（CCR）患者n = 20，疾病后期复发患者n = 15）中IGF-I、-II以及IGFBP-2、-3的mRNA表达谱。来自健康供者外周血和骨髓的单个核细胞（MNC）样本用作对照。
AML细胞中IGFBP-2的表达显著高于外周MNC的健康细胞（P < 0.001）和骨髓细胞（P < 0.01）。相反，与对照相比，AML细胞中IGFBP-3和IGF-I基因的表达显著降低（P = 0.02；P < 0.001）。疾病后期复发的患者（中位数±范围：0.0929±0.049）在诊断时的IGFBP-2表达高于CCR患者（0.0121±0.047；P = 0.06）。多因素分析确定IGFBP-2 mRNA表达是预测复发的独立因素。此外，IGFBP-2 mRNA水平>0.1000的患者无复发生存（RFS）概率为28%；而IGFBP-2 mRNA水平<0.1000的患者RFS概率为62%（P = 0.04，对数秩检验）。未发现其他研究基因有预后影响。
结果表明正常细胞与AML细胞之间IGF成分的表达不同。IGFBP-2 mRNA水平高达0.1000（相对于KG1细胞系）的患者更易复发。在诊断时识别这些患者可能有助于实现更个体化的治疗。
