Serum levels of insulin-like growth factor-I, -II and insulin-like growth factor binding proteins -2 and -3 in children with acute lymphoblastic leukaemia

Abstract

The insulin-like growth factor (IGF) signaling pathway may be of importance for the proliferation of different tumours (e.g. breast cancer and Wilms tumour). The bioavailability of both IGF-I and IGF-II is regulated by specific IGF-binding proteins (IGFBPs). IGFBP-2 is the predominant binding protein during fetal life, where it is expressed in most tissues. In contrast, postnatally it is mainly released by specific cell types (hepatocytes, astroglia, kidney cells, prostate cells) and a range of tumour cell lines. Furthermore, phytohaemagglutinin stimulated normal lymphoblasts and malignant lymphoblasts express IGFBP-2. In order to investigate the IGF regulatory pathway in leukaemia serum levels of IGF-I, IGF-II, IGFBP-2 and IGFBP-3 were determined in 28 leukaemic children. Whereas serum levels of IGF-I (mean/range: -2.7/-0.1 to -6.7 SDS), IGF-II (-3.6 SDS/-1.3 to -8.7) and IGFBP-3 (-2.0/+2.2 to -7.1 SDS) were significantly decreased comparable to levels in growth hormone deficiency, IGFBP-2 levels (+4.0/-0.45 to +7.4 SDS) were found to be markedly elevated and inversely correlated to IGF-I (r = -0.51, P = 0.013). After haematological remission upon chemotherapy all four parameters had normalized in the 16 re-investigated children. Similar findings have been observed in one boy with a relapse including CNS leukaemia.

Conclusion: This study demonstrates that the proliferation of malignant lymphoblasts (at diagnosis vs treatment) occurs in the presence of decreased serum levels of IGF-I, IGF-II and IGFBP-3 and that diminished production of these peptides may contribute to impaired growth. It further indicates that serum levels of IGFBP-2 may be directly related to the proliferation of lymphoblasts.