Knocking out cancer cells in Leukemia

Cancer initiating cells (CICs) or leukemia initiating cells (LICs) are stealth populations impervious to conventional chemotherapy and resistant to targeted cancer therapies. When a leukemia patient relapses following a period of remission, it is the LICs that are the cause of the disease’s re-emergence.

Researchers at the Beth Israel Deaconess Medical Center (BIDMC) have found that a tumour 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. They suggest that inhibition of PML is a promising target for new agents.

Their findings, which appear in Nature, also demonstrate that PML can be degraded with an arsenic-based agent called arsenic trioxide, which has been used in traditional Chinese medicine. When combined with chemotherapy, the arsenic-based therapy, already proven safe and non-toxic in clinical trials for a rare form of leukemia called Acute Promyelocytic Leukemia (APL) can also potentially treat the more common Chronic Myeloid Leukemia (CML) and reduce risk of relapse.

The concept is a very simple one; 90% of existing cancer treatments are anti-proliferative agents. They target the pool of proliferative cells, leaving behind the dormant LICs. By knocking out the quiescent cells with arsenic trioxide, the risk of relapse is much reduced. This approach might be useful in other treatment approaches for different leukemias.

Cancer intelligence - cytogenetic abnormalities in AML

Cytogenetic abnormalities are long been useful in guiding treatment for acute myeloid leukemia (AML). One of the crucial questions in the treatment algorithm is whether or not an allogeneic stem-cell transplant is an option. Transplantation can be a curative treatment for AML, but it carries risks, including transplant related mortality and morbidity. Currently, it is usually considered for AML when the cytogenetic abnormalities foretell a high risk for relapse after chemotherapy and avoided when there is a cytogenetic pattern that is associated with a relatively favorable prognosis.

New details of differences among patients with cytogenetically normal AML, which appear to affect both clinical and treatment outcome, are described in 2 papers published in the May 1 issue of the New England Journal of Medicine. One paper describes new gene mutations, and the other outlines microarray microRNA expression profiles. Both studies demonstrate the complex molecular heterogeneity of AML and may add to the accumulating knowledge about the way genetic disruptions in AML can affect prognosis.