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

Abstract

BACKGROUND:

Insulin-like growth factor (IGF) system as regulator for cellular proliferation is of particular interest in search for new prognostic approaches in cancer treatment.

PROCEDURE:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Kristin Dawczynski, Daniel Steinbach, Susann Wittig, Nadine Pfaffendorf, Eberhard Kauf, Felix Zintl
• Journal: Pediatric blood & cancer (Pediatr Blood Cancer) Vol. 50 Issue 1 Pg. 24-8 (Jan 2008) ISSN: 1545-5017 [Electronic] United States
• PMID: 17635002 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2007 Wiley-Liss, Inc.

Chemical References

• Insulin-Like Growth Factor Binding Protein 2
• Insulin-Like Growth Factor Binding Protein 3
• RNA, Messenger
• Insulin-Like Growth Factor I
• Insulin-Like Growth Factor II

Topics

• Child
• Disease-Free Survival
• Gene Expression
• Humans
• Insulin-Like Growth Factor Binding Protein 2 (genetics, metabolism)
• Insulin-Like Growth Factor Binding Protein 3 (genetics, metabolism)
• Insulin-Like Growth Factor I (genetics, metabolism)
• Insulin-Like Growth Factor II (genetics, metabolism)
• Leukemia, Myeloid, Acute (genetics, metabolism, mortality)
• RNA, Messenger (metabolism)