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

Huey Kiam How, Allen Yeoh, Thuan Chong Quah, Youngman Oh, Ronald (Ron) Rosenfeld, Kok Onn Lee

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1283-1287
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume84
Issue number4
StatePublished - 1999

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Insulin-Like Growth Factor Binding Protein 6
Cerebrospinal fluid
Insulin-Like Growth Factor Binding Proteins
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Cerebrospinal Fluid
Insulin-Like Growth Factor Binding Protein 3
Insulin-Like Growth Factor Binding Protein 2
Western Blotting
Meningitis
Leukemia
Ligands
Febrile Seizures
Chemotherapy
insulin-like growth factor binding protein-related protein 1
Immunoassay
Level control
Neurology
Therapeutics
Central Nervous System
Drug Therapy

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Insulin-like growth factor binding proteins (IGFBPs) and IGFBP-related protein 1-levels in cerebrospinal fluid of children with acute lymphoblastic leukemia. / How, Huey Kiam; Yeoh, Allen; Quah, Thuan Chong; Oh, Youngman; Rosenfeld, Ronald (Ron); Lee, Kok Onn.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 84, No. 4, 1999, p. 1283-1287.

Research output: Contribution to journalArticle

How, Huey Kiam ; Yeoh, Allen ; Quah, Thuan Chong ; Oh, Youngman ; Rosenfeld, Ronald (Ron) ; Lee, Kok Onn. / Insulin-like growth factor binding proteins (IGFBPs) and IGFBP-related protein 1-levels in cerebrospinal fluid of children with acute lymphoblastic leukemia. In: Journal of Clinical Endocrinology and Metabolism. 1999 ; Vol. 84, No. 4. pp. 1283-1287.
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abstract = "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.",
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AU - Rosenfeld, Ronald (Ron)

AU - Lee, Kok Onn

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N2 - 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.

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