Summary Chronic lymphocytic leukaemia (CLL) is characterized by the accumulation of long‐lived B lymphocytes blocked in G0/1 by impaired apoptosis. As insulin‐like growth factor‐I (IGF‐I) is known for its antiapoptotic effects in different cell types, we investigated whether IGF‐I and its receptor (IGF‐IR) participate in autocrine/paracrine loops affecting the survival of CLL cells. IGF‐IR protein and mRNA was present in CLL cells in 44% and 59% of patients respectively. IGF‐IR expression in CLL patients was positively correlated with the expression of the antiapoptotic protein Bcl‐2 and was involved in CLL cell survival in vitro. Serum IGF‐I was elevated in CLL patients, but growth hormone (GH) was normal. CLL cells expressed IGF‐I mRNA and secreted the growth factor in vitro. Therefore, local production of IGF‐I can account for the increased levels of serum IGF‐I, independently of GH, and may be related to autocrine/paracrine control of lymphocyte survival acting at IGF‐IR. This is the first demonstration of IGF‐IR expression in a subgroup of CLL patients and of its antiapoptotic effects in vitro, highlighting the importance of this growth factor receptor as a possible therapeutic target in CLL.

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Objective: To investigate the kinetics of insulin-like growth factor-1 receptor (IGF-1R) expression in PHA-stimulated T lymphocytes. Methods: IGF-1R protein and mRNA were detected by flow cytometry and RT-PCR respectively, between 0 and 48 h after cell activation. Results: Few minutes after T lymphocytes were activated, internalization of the IGF-1R from the cell membrane was observed, achieving the lower level between 1 and 6 h and was accompanied by a reduction in its mRNA. This was followed by re-expression of IGF-1R on the cell surface and an increase in IGF-1R mRNA levels in the cytoplasm, reaching levels higher than those recorded initially after 48 h activation. Conclusion: This down- and up-regulation suggests that restoration of IGF-1R would be the result of receptor recycling and de novo synthesis and highlights its importance for T lymphocyte proliferation.