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Arsenic-based therapy shown to help eradicate leukemia-initiating cells
Date:5/12/2008

BOSTON -- In both leukemia and solid tumors, there exists among the multitude of warrior cancer cells a small subgroup that work undercover, patiently lying in wait to launch their attacks. Known as either cancer initiating cells (CICs) or leukemia initiating cells (LICs), these stealth populations are impervious to conventional chemotherapy and undaunted by targeted cancer therapies. When a leukemia patient relapses following a period of remission, it is the LICs that bear responsibility for the diseases reemergence.

The secret to the survival abilities of these cells has been unclear. But in a paradoxical discovery, a research team led by investigators at Beth Israel Deaconess Medical Center (BIDMC) has found that a tumor suppressor protein known as PML appears to be the factor that enables LICs to maintain their quiescence the inert state that protects them from being destroyed by cancer therapies and suggests that inhibition of PML is a promising target for new therapeutics.

Their findings, which appear in todays advance on-line issue of the journal Nature, additionally demonstrate that PML can be degraded with an arsenic-based agent used in traditional Chinese medicine. Importantly, when combined with chemotherapy, the arsenic-based therapy -- already proven safe and non-toxic in clinical trials -- can successfully treat chronic myeloid leukemia.

Leukemia initiating cells share many properties of normal hematopoetic stem cells, explains senior author Pier Paolo Pandolfi, MD, PhD, Director of the Cancer Genetics Program in BIDMCs Cancer Center and Professor of Medicine and of Pathology at Harvard Medical School. They are pluripotent, they readily replicate and they can indefinitely remain in a dormant state of quiescence.

Consequently, while the majority of leukemic cells are vulnerable to any cancer therapies including chemotherapy and targeted cancer treatments that destroy cells during active DNA replication, L
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Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
Source:Eurekalert

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