SERUM LEVELS OF INSULIN-LIKE GROWTH-FACTOR-I, GROWTH-FACTOR-II AND INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEIN-2 AND BINDING-PROTEIN-3 IN CHILDREN WITH ACUTE LYMPHOBLASTIC-LEUKEMIA

The insulin-like growth factor (IGF) signaling pathway may be of impor tance for the proliferation of different tumours (e.g. breast cancer a nd Wilms tumour). The bioavailability of both IGF-I and IGF-II is regu lated by specific IGF-binding proteins (IGFBPs). IGFBP-2 is the predom inant binding protein during fetal life, where it is expressed in most tissues. In contrast, postnatally it is mainly released by specific c ell types (hepatocytes, astroglia, kidney cells, prostate cells) and a range of tumour cell lines. Furthermore, phytohaemagglutinin stimulat ed normal lymphoblasts and malignant lymphoblasts express IGFBP-2. In order to investigate the IGF regulatory pathway in leukaemia serum lev els of IGF-I, IGF-II, IGFBP-2 and IGFBP-3 were determined in 28 leukae mic children. Whereas serum levels of IGF-I (mean/range: -2.7/-0.1 to -6.7 SDS), IGF-TI(-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 hor mone 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 pa rameters had normalized in the 16 re-investigated children. Similar fi ndings have been observed in one boy with a relapse including CNS leuk aemia. Conclusion This study demonstrates that the proliferation of ma lignant lymphoblasts (at diagnosis vs treatment) occurs in the presenc e of decreased serum levels of IGF-I, IGF-II and IGFBP-3 and that dimi nished production of these peptides may contribute to impaired growth. It further indicates that serum levels of IGFBP-2 may be directly rel ated to the proliferation of lymphoblasts.