Insulin-like Growth Factor-Binding Protein 4 in Children with Acute Lymphoblastic Leukemia

• Published in: International journal of hematology Vol. 82; no. 2; pp. 137 - 142
• Main Authors: Wex, Heike, Ahrens, Dörte, Hohmann, Bianka, Redlich, Antje, Mittler, Uwe, Vorwerk, Peter
• Format: Journal Article
• Language: English
• Published: Tokyo Springer 01.08.2005; Springer Nature B.V
• Subjects: Adolescent; Adult; Biological and medical sciences; Child; Child, Preschool; Female; Gene Expression Regulation, Leukemic; Hematologic and hematopoietic diseases; Humans; Infant; Insulin-Like Growth Factor Binding Protein 4 - blood; Insulin-Like Growth Factor Binding Protein 4 - genetics; Insulin-Like Growth Factor I - analysis; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Tumor Cells, Cultured; Human; Insulin-like growth factor binding protein-4; Hematology; Acute lymphoblastic leukemia; IGFBP-4; Lymphoproliferative syndrome; Acute; Acute leukemia; Malignant hemopathy; Acute lymphocytic leukemia; Children; Child
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1532/IJH97.E0429

Insulin-like growth factor-binding protein 4 (IGFBP-4) is a potent inhibitor of IGF-mediated cell proliferation. To investigate the functional relevance of IGFBP-4 in leukemia, we measured plasma IGFBP-4 levels and messenger RNA expression in leukemic cell clones of patients with acute lymphoblastic leukemia (ALL) and in control subjects. The IGFBP-4 levels of ALL patients at diagnosis were significantly lower than the levels of healthy control subjects. We evaluated the patients at diagnosis and after 33 days of chemotherapy and found plasma IGFBP-4 levels at day 33 to be significantly lower than the levels at diagnosis. There was no correlation of plasma IGFBP-4 level with age, sex, immunophenotype, or ALL risk group, and there was no correlation of IGFBP-4 level with plasma IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3 levels. Gene expression analysis of the leukemic blast population at diagnosis revealed that the leukemic clones did not significantly contribute to systemic IGFBP-4 levels. The decrease in plasma IGFBP-4 levels during chemotherapy represents an indirect effect, probably caused by the chemotherapeutic effects on IGFBP-4-expressing cells of the liver and other organs. In addition, IGFBP-4 gene expression was investigated in 13 human immune cell-related cell lines by reverse transcription-polymerase chain reaction analysis. IGFBP-4 was exclusively expressed in cell lines derived either from B-cells or from myelomonocytic cells, whereas IGFBP-4 was not expressed in T-cell lines.