Trial Information

Phase I Study to Evaluate the Safety of Zileuton (Zyflo) in Combination With Imatinib Mesylate (Gleevec) in Patients With Chronic Myelogenous Leukemia

More than twenty two thousand people live with chronic myelogenous leukemia in the United
States and more than five thousand people are expected to be diagnosed this year. The
majority of patients with this disease are diagnosed in what is called the chronic phase.
The standard treatment for this phase of the disease is therapy with a medication called
imatinib. This treatment can diminish the amount of disease to very low levels that only
very sensitive and specialized techniques can measure; it does not, however, provide a cure.

Dr. Shaoguang Li and colleagues at University of Massachusetts have published a unique
discovery that the arachidonate 5-lipoxygenase (5-LO) gene (Alox5) is a critical regulator
for LSCs in BCR-ABL-induced CML (Chen Y et al. Loss of the Alox5 gene impairs leukemia stem
cells and prevents chronic myeloid leukemia. Nature Genetics 41:783-792, 2009). In the
absence of Alox5, BCR-ABL failed to induce CML in preclinical studies. While deficiency in
Alox5 had no effect on normal hematopoiesis, impairment of the LSCs function through
differentiation and cell division of CML LSCs was observed. This defect led to a depletion
of LSCs and a failure of CML development. Treatment with a 5-LO inhibitor (zileuton) also
impaired the function of LSCs and prolonged survival. These results demonstrate that a
specific target gene can be found in cancer stem cells and its inhibition can completely
inhibit the function of these stem cells. These findings provide an exciting opportunity to
develop the first anti-cancer stem cell therapy for treating CML.