Autocrine/paracrine involvement of insulin‐like growth factor‐I and its receptor in chronic lymphocytic leukaemia

• Published in: British journal of haematology 2005-07, Vol.130 (1), p.58-66
• Main Authors: Schillaci, Roxana, Galeano, Adriana, Becu‐Villalobos, Damasia, Spinelli, Olga, Sapia, Sandra, Bezares, Raimundo F.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Analysis of Variance; Apoptosis; Autocrine Communication; B cells; B-Lymphocytes - chemistry; B-Lymphocytes - metabolism; Biological and medical sciences; Case-Control Studies; chronic lymphocytic leukaemia (CLL); CLL apoptosis; CLL growth factors; Culture Media, Conditioned - chemistry; Female; Flow Cytometry; Growth Hormone - blood; Hematologic and hematopoietic diseases; Hematology; Humans; Insulin-Like Growth Factor I - analysis; Insulin-Like Growth Factor I - genetics; Insulin-Like Growth Factor I - metabolism; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Paracrine Communication; Receptor, IGF Type 1 - analysis; Receptor, IGF Type 1 - genetics; Receptor, IGF Type 1 - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Tumor Cells, Cultured
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2005.05579.x

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.