TK Inhibitor Treatment Disrupts Growth Hormone Axis: Clinical Observations in Children with CML and Experimental Data from a Juvenile Animal Model
| Autor: | Roland Jung, Ingmar Glauche, Anna Ulmer, J. Tabea Tauer, M Suttorp |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Adolescent medicine.medical_treatment Antineoplastic Agents Piperazines Leukemia Myelogenous Chronic BCR-ABL Positive hemic and lymphatic diseases Internal medicine medicine Animals Humans Juvenile animal Insulin-Like Growth Factor I Rats Wistar Child Protein Kinase Inhibitors Bone growth Bone Development business.industry Growth factor Imatinib Body Height Rats Dasatinib Disease Models Animal Insulin-Like Growth Factor Binding Protein 3 Pyrimidines Imatinib mesylate Endocrinology Animals Newborn Benzamides Pediatrics Perinatology and Child Health Imatinib Mesylate Female business Bosutinib Tyrosine kinase Follow-Up Studies medicine.drug |
| Zdroj: | Klinische Pädiatrie. 225:120-126 |
| ISSN: | 1439-3824 0300-8630 |
| DOI: | 10.1055/s-0033-1343483 |
| Popis: | Long-term treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKIs) exerts off-target effects on bone growth by either impaired growth hormone (GH) action or osseous modelling impairment. Body height and the GH-related parameters insulin-like growth factor 1 (IGF-1) and insulin-like growth factor-binding protein 3(IGFBP-3) were determined repetitively 3-monthly over 2 years in 21 pediatric CML-patients on standardized imatinib treatment. In an animal model 4-week-old male Wistar rats were exposed over 10 weeks to imatinib, dasatinib, or bosutinib at varying concentrations via the drinking water. Blood was collected at prepubertal age, pubertal age, and at adult age, respectively, and animals’ serum levels of IGFBP-3 were measured. Independent from treatment duration patients exhibited IGF-1 and IGFBP-3 levels almost exclusively in the very low range when compared to age-matched references. No clear pattern of rising or falling IGF-1 and IGFBP-3 levels was observed. In rats, compared to controls, serum IGFBP-3 was significantly lowered for all TKIs tested, at all concentrations applied, and at all ages under investigation. Besides direct off-target effects on the growing skeleton, TKI treatment also results in lowered blood levels of IGF-1 and IGFBP-3. A juvenile rat model predicts this side effect for dasatinib and bosutinib. Thus, growth and GH- related parameters should be monitored regularly in pediatric patients with CML on TKIs. |
| Databáze: | OpenAIRE |
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