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April 12, 2005
Valproic acid may increase chemotherapy response
Topics:Summary:
Valproic acid affects healthy hematopoietic stem cells in a manner that is distinctly different
from that exerted on leukemic cells. Reporting in the April 1st issue
of Cancer Research, German researchers suggest that by stimulating
proliferation of hematopoietic stem cells, valproic acid could increase
cancer patients' response to conventional chemotherapy.
Of Interest:
Valproic acid is a histone deacetylase inhibitor previously suggested for treatment of acute myeloid leukemia and other cancers. Studies have shown that the agent selectively induces differentiation and apoptosis
of leukemia cells. Histone deacetylase inhibitors have attracted
considerable attention because of their ability to overcome the
differentiation block in leukemic blasts, an effect achieved either
alone or in combination with differentiating agents, such as all-trans
retinoic acid. Studies have also shown that valproic acid, known to
induce differentiation or apoptosis in leukemic blasts, stimulates the
proliferation of normal hematopoietic stem cells, an effect with a
potential effect on its future role in the treatment of acute myeloid
leukemia.
(...) The research team, led by Dr. Martin Ruthardt, has found that "patients responding to this therapy frequently developed constant or increased bone marrow cellularity despite a remarkable blast cell reduction and peripheral hypergranulocytosis."
(...) For their current report, Dr. Ruthardt and colleagues at Klinikum der Johann Wolfgang Goethe-Universitat in Frankfurt investigated the effects of valproic acid on normal cultured hematopoietic stem cells.
(...) In contrast to AML cells, valproic acid increased the proliferation of human CD34+ HSCs, but prevented them from differentiating into CD14+ cells.
(...) "The valproic acid-induced entry of quiescent hematopoietic and leukemic stem cells into the cell cycle could render them more susceptible to conventional chemotherapy, resulting either in a prolonged aplasia due to a higher efficiency of the therapy or in a shortened aplasia owing to the enforced proliferation of the normal hematopoiesis," Dr. Ruthardt's team concludes.
Related readings:
Acute leukemia associated with valproic acid treatment: A novel mechanism for leukemogenesis?
Valproic acid induces apoptosis and cell cycle arrest in poorly differentiated thyroid cancer cells.
Valproic acid induces differentiation of a supratentorial primitive neuroectodermal tumor.
Cross posted at NewHopeBlog
Posted by Hyscience at April 12, 2005 12:40 PM
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