Insulin-like growth factor binding proteins (IGFBPs) and IGFBP-related protein 1-levels in cerebrospinal fluid of children with acute lymphoblastic leukemia

Abnormalities in insulin-like growth factor binding proteins (IGFBPs) have been reported in the cerebrospinal fluid (CSF) of children with acute leuke mia. In the present study, we have further characterized the IGFBPs in whol e CSF prospectively in II children with acute B-lineage lymphoblastic leuke mia (ALL) undergoing chemotherapy. Western ligand blots Western immunoblots using a new anti-IGFBP-6 and a new IGFBP-rP1 (related protein-1 antibody a nd immunoassays (Diagnostic Systems Laboratories, Inc., Webster, TX) were u sed to characterize and measure IGFBP-6, IGFBP-2, IGFBP-3, and IGFBP-rP1 in children with ALL at diagnosis, and with treatment. Comparisons at baselin e were made with 11 children with meningitis and II children with febrile c onvulsions (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 I GFBP-3 was elevated in ALL patients, 29 (+/- 9) ng/mL; compared with mening itis, 11 (+/- 1) ng/mL; and controls, 10(+/- 1) ng/mL (P < 0.05, t test); a nd IGFBP-2 did not differ among the three groups (47-59 ng/mL, P > 0.05). C SF 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 no t change significantly. At baseline, Western ligand blots and Western immun oblots identified a 25- to 28-kDa broad band as IGFBP-6 and a 30-kDa band a s 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, comp ared 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 a cute leukemia remain to be further elucidated.