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Acute leukemia associated with valproic acid treatment: A novel mechanism for leukemogenesis?
Author(s) -
Coyle Thomas E.,
Bair Alicia K.,
Stein Constance,
Vajpayee Neerja,
Mehdi Syed,
Wright Jonathan
Publication year - 2005
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.20273
Subject(s) - valproic acid , histone deacetylase inhibitor , histone deacetylase , cancer research , leukemia , medicine , histone , biology , genetics , dna , epilepsy , psychiatry
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. Am. J. Hematol. 78:256–260, 2005. © 2005 Wiley‐Liss, Inc.