Expression of components of the IGF axis in childhood acute myelogenous leukemia

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.