Closing in on the Leukemia Cure

Why chronic myeloid leukemia stem cells are resistant to cancer drugs

/ Author:  / Reviewed by: Joseph V. Madia, MD

(RxWiki News) The majority of patients with chronic myeloid leukemia recover using various cancer drug treatments. However, they are not cured, as a type of cancerous stem cell is resistant to the drugs.

Now, researchers have found what allows these cells to remain alive, bringing us closer to a cure.

Currently, chronic myeloid leukemia - a type of blood and bone marrow cancer - is treated using a class of drugs called tyrosine kinase inhibitors. About 90 percent of patients recover from the cancer using these drugs.

However, stem cells of the cancer - which are resistant to drug treatment - remain alive, putting patients at risk of developing the cancer again.

Researchers have discovered that these cancerous stem cells are resistant to drug treatment because they go into autophagy - a state in which the cells shut down and survive on nutrients within the cell, making it impossible for tyrosine kinase inhibitors to kill them.

In search of a cure, researchers now are testing drugs known to kill cells in a state of autophagy.

dailyRx Insight: If scientists figure out a way to kill these cancerous stem cells, then we may have found a cure for chronic myeloid leukemia.

A team of researchers - led by Tessa Holyoake, a professor at the University of Glasgow - is in the process of testing a drug called hydroxychloroquine on patients who still show evidence of chronic myeloid leukemia, even after being treated with tyrosine kinase inhibitors.

They are testing hydroxychloroquine - a drug used to treat malaria as well as rheumatoid arthritis - because it is known to kill cells that are in a state of autophagy.

According to Holyoake, hydroxychloroquine may not be the best drug for the job, as long-term treatment has some serious side effects, including temporary or permanent eye problems. However, she says, this study may show that using this type of drug works in principle.

If that is the case, then researchers can start to quickly explore new treatment options that might provide a cure for those patients in which tyrosine kinase inhibitors are not a full cure.

Chronic myelogenous leukemia affects 20,000 people in the United States, but about 4,500 are newly diagnosed each year. It is the result of a genetic mutation that causes white blood cell production to increase out of control. At first, during the chronic phase, the body produces too many white blood cells. If untreated, it progresses to the accelerated and then blast phases, where the production of immature, non-functioning white cells overwhelms the body, leaving patients susceptible to infection, anemia, and death. The chronic phase may be asymptomatic, with diagnosis being made from a routine blood test. Symptoms of the accelerated phase include night sweats, fatigue, easy bruising, fever, and infections. Treatment is with drugs called tyrosine kinase inhibitors (Gleevec, Sprycel, Tasigna), and recent statistics show an 89% five year survival rate from their use. 

Professor Tessa Holyoake spoke about her team's ongoing research at the conference of the UK National Stem Cell Network.

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Review Date: 
March 31, 2011
Last Updated:
November 8, 2012