Acute leukemia associated with valproic acid treatment: A novel mechanism for leukemogenesis?
| Autor: | Alicia K. Bair, Neerja Vajpayee, Syed Mehdi, Thomas Coyle, Jonathan Wright, Constance K. Stein |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Male medicine.drug_class DNA damage Trisomy 8 Myelogenous hemic and lymphatic diseases Humans Medicine Chromosome Aberrations Valproic Acid Acute leukemia Epilepsy Leukemia business.industry Histone deacetylase inhibitor Hematology medicine.disease Acute Disease Immunology Cancer research Anticonvulsants Female lipids (amino acids peptides and proteins) Histone deacetylase Chromosomes Human Pair 9 business Chromosomes Human Pair 7 Gene Deletion DNA Damage medicine.drug |
| Zdroj: | American Journal of Hematology. 78:256-260 |
| ISSN: | 1096-8652 0361-8609 |
| DOI: | 10.1002/ajh.20273 |
| Popis: | Valproic acid has been previously associated with hematologic toxicity, including a reversible myelodysplasia-like syndrome without chromosomal abnormalities. We now report three cases of acute leukemia with features of secondary leukemia associated with valproic acid therapy: two cases of acute myelogenous leukemia with multilineage dysplasia, one with trisomy 8 and one with monosomy 7, and one case of secondary acute lymphoblastic leukemia with del (7) (q22q34), del (9) (q21.11q22), del (11) (q12q23). One patient had a previous myelodysplastic syndrome while on valproic acid. Valproic acid has been previously shown to be a histone deacetylase inhibitor. Inhibition of histone deacetylase causes a relaxation of chromatin structure and thus increases susceptibility to DNA damage and sensitizes cells to radiation. We propose that valproic acid therapy may lead to secondary leukemia by increasing DNA damage through chronic inhibition of histone deacetylase. |
| Databáze: | OpenAIRE |
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