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April 12, 2005

Valproic acid may increase chemotherapy response

Topics: Clinical Pharmacology

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.

Read more ...

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.

Posted by Richard at April 12, 2005 11:33 AM

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