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Insulin-Like Growth Factor Binding Proteins (IGFBPs) and IGFBP-Related Protein 1-Levels in Cerebrospinal Fluid of Children with Acute Lymphoblastic Leukemia¹

Department of Medicine (H.K.H., K.-O.L.), Department of Pediatrics (A.Y., T.C.Q.), National University of Singapore, Singapore 119074; and Department of Pediatrics (Y.O., R.G.R.), Oregon Health Sciences University, Portland, Oregon 97201

Address all correspondence and requests for reprints to: K. O. Lee, Division of Endocrinology, Department of Medicine, 10 Kent Ridge Crescent, Singapore 119074. E-mail: mdcleeko{at}nus.edu.sg

Abnormalities in insulin-like growth factor binding proteins (IGFBPs) have been reported in the cerebrospinal fluid (CSF) of children with acute leukemia. In the present study, we have further characterized the IGFBPs in whole CSF prospectively in 11 children with acute B-lineage lymphoblastic leukemia (ALL) undergoing chemotherapy. Western ligand blots Western immunoblots using a new anti-IGFBP-6 and a new IGFBP-rP1 (related protein-1 antibody and immunoassays (Diagnostic Systems Laboratories, Inc., Webster, TX) were used to characterize and measure IGFBP-6, IGFBP-2, IGFBP-3, and IGFBP-rP1 in children with ALL at diagnosis, and with treatment. Comparisons at baseline were made with 11 children with meningitis and 11 children with febrile convulsions (controls). The mean (± SE) CSF IGFBP-6 in ALL patients, 56 (± 7) ng/mL, was significantly lower than in meningitis, 97 (± 17) ng/mL; and in controls, 123 (± 24) ng/mL (P < 0.05, t test). In contrast, CSF IGFBP-3 was elevated in ALL patients, 29 (± 9) ng/mL; compared with meningitis, 11 (± 1) ng/mL; and controls, 10 (± 1) ng/mL (P < 0.05, t test); and IGFBP-2 did not differ among the three groups (47–59 ng/mL, P > 0.05). CSF IGFBP-6 remained very low in the patients with ALL, at 4 and 36 weeks of treatment; whereas IGFBP-3 decreased to control levels, and IGFBP-2 did not change significantly. At baseline, Western ligand blots and Western immunoblots identified a 25- to 28-kDa broad band as IGFBP-6 and a 30-kDa band as IGFBP-2 and showed that there was almost no intact IGFBP-3 in CSF. IGFBP-rP1 was also present in the CSF and was elevated in patients with ALL, compared with the 2 control groups. In conclusion, at diagnosis, IGFBP-rP1 and fragments of IGFBP-3 are elevated, and IGFBP-6 is significantly decreased, in the CSF of ALL children; and IGFBP-6 remained low, with treatment, up to 36 weeks. The role of the IGFBPs and IGFBP-rPs in central nervous system acute leukemia remain to be further elucidated.