Omacetaxine has potential to treat resistant leukemia

NEW YORK (Reuters Health) - Omacetaxine inhibits leukemic stem cells and is effective against BCR-ABL-induced chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) in mice, according to a report in the March 26th advance online publication of Leukemia.

"Eradicating cancer stem cells is required for curing cancers," Dr. Shaoguang Li from the University of Massachusetts Medical School, Worcester, told Reuters Health. "All available BCR-ABL kinase inhibitors are unable to kill leukemia stem cells, and omacetaxine is one drug that is available clinically and has an inhibitory effect on leukemia stem cells."

Dr. Li and colleagues used myelogenous and lymphoid cells lines to investigate the effect of omacetaxine, as well as a mouse model of CML and B-cell ALL.

"We showed that more than 90% of leukemic stem cells were killed after treatment with omacetaxine in vitro," the researchers report. "In contrast, less than 9% or 25% of the leukemic cells were killed after treating with imatinib or dasatinib, respectively."

In mice with CML, omacetaxine treatment suppressed leukemia stem cells, reduced splenomegaly, and improved survival. Similarly, omacetaxine reduced peripheral blood B-leukemia cells and improved survival in mice with B-ALL.

The researchers observed that, in myeloid leukemia cells, omacetaxine degraded BCR-ABL protein through inhibiting HSP90, whereas omacetaxine inhibited BCR-ABL expression in B-leukemia cells without affecting HSP90 protein levels.

Dr. Li outlined the next steps in evaluating omacetaxine: "We will transplant bone marrow cells from CML patients or BCR-ABL transduced human cord blood stem cells into NOD/SCID mice, and treat the mice with omacetaxine to evaluate its inhibitory effect on human CML stem cells. For ALL, we will transplant bone marrow cells from ALL patients into NOD/SCID mice, and treat the mice with the drug to evaluate its effect on ALL."

"There is an urgent need for studying the biology of cancer stem cells to develop anti-stem cell therapies for curing cancers," Dr. Li added.

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