Overcoming multidrug resistance in acute lymphoblastic leukemia cells

March 2, 2010, Journal of Clinical Investigation

A strong predictor of poor outcome in children with acute lymphoblastic leukemia (ALL) is resistance to chemotherapy with glucocorticoids. Such resistance is caused, in part, by an inability of the leukemic cells to die by a process known as mitochondrial apoptosis. However, researchers have now identified a way to get round this block in mitochondrial apoptosis in glucocorticoid-resistant childhood ALL cells.

Acute lymphoblastic leukemia (ALL) most commonly affects children, in whom there is an overall cure rate of 85%. A strong predictor of poor outcome is resistance to with glucocorticoids. Such resistance is caused, at least in part, by an inability of the leukemic cells to die by a process known as mitochondrial apoptosis. Many researchers are therefore trying to find ways to overcome the block in mitochondrial apoptosis in glucocorticoid-resistant leukemic cells. Jean-Pierre Bourquin and colleagues, at the University of Zurich, Switzerland, have now identified a way to do just that, showing that this approach resensitizes multidrug-resistant childhood ALL cells to glucocorticoids and other cytotoxic agents.

The authors found that treating multidrug-resistant childhood ALL cells with the drug obatoclax, which is under development for the treatment of both and , resensitized them to glucocorticoids and other cytotoxic agents. Further analysis indicated that this reversal of glucocorticoid resistance occurred through rapid activation of a process known as autophagy-dependent necroptosis, bypassing the block in mitochondrial apoptosis.

As the levels of obatoclax required to achieve these effects were not themselves toxic to the cells, the authors suggest that their data provide the rationale for treating individuals with multidrug-resistant ALL in a similar way.

More information: Induction of autophagy-dependent necroptosis is required for childhood acute lymphoblastic leukemia cells to overcome glucocorticoid resistance, www.jci.org/articles/view/3998 … 4e895dead848910ba5a2

Related Stories

Recommended for you

Colon cancer is caused by bacteria and cell stress

September 19, 2018
Researchers at Technical University Munich have reported findings related to the development of colon cancer. "We originally wanted to study the role of bacteria in the intestines in the development of intestinal inflammation," ...

Researchers find adult stem cell characteristics in aggressive cancers from different tissues

September 19, 2018
UCLA researchers have discovered genetic similarities between the adult stem cells responsible for maintaining and repairing epithelial tissues—which line all of the organs and cavities inside the body—and the cells that ...

Ketogenic diet reduces body fat in women with ovarian or endometrial cancer

September 19, 2018
Women with ovarian or endometrial cancer who followed the ketogenic diet for 12 weeks lost more body fat and had lower insulin levels compared to those who followed the low-fat diet recommended by the American Cancer Society, ...

Eating foods with low nutritional quality ratings linked to cancer risk in large European cohort

September 18, 2018
The consumption of foods with higher scores on the British Food Standards Agency nutrient profiling system (FSAm-NPS), reflecting a lower nutritional quality, is associated with an increased risk of developing cancer, according ...

Could the zika virus fight the brain cancer that killed john McCain?

September 18, 2018
(HealthDay)—Preliminary research in mice suggests that the Zika virus might be turned from foe into friend—enlisted to curb deadly glioblastoma brain tumors.

CRISPR screen reveals new targets in more than half of all squamous cell carcinomas

September 18, 2018
A little p63 goes a long way in embryonic development—and flaws in p63 can result in birth defects like cleft palette, fused fingers or even missing limbs. But once this early work is done, p63 goes silent, sitting quietly ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.