Navigation Links
Researchers find leukemia cells metabolize fat to avoid cell death
Date:1/27/2010

HOUSTON - Leukemia cells, like most cancers, are addicted to glucose to generate their energy, but new research shows for the first time that these cells also rely on fatty acid metabolism to grow and to evade cell death.

Inhibiting fatty acid oxidation makes leukemia cells vulnerable to drugs that force them to commit suicide, scientists from The University of Texas M. D. Anderson Cancer Center and The University of Texas Medical School at Houston report in the January edition of the Journal of Clinical Investigation.

"These findings translate to a potentially transformational approach to controlling leukemia and cancer cell metabolism by therapeutically targeting fatty acid oxidation," said co-senior author Michael Andreeff, M.D., Ph.D., professor in M. D. Anderson's Department of Stem Cell Transplantation and Cellular Therapy.

"Cancer metabolism has attracted renewed, cutting-edge research interest," Andreeff said. "Here we have first identified a metabolic target and our first in vivo results are promising, but there is much more work that needs to be done."

Andreeff and co-senior author Heinrich Taegtmeyer, M.D., D.Phil., professor in the University of Texas Medical School Division of Cardiovascular Medicine, are collaborating to develop drugs based on their research results.

"The leukemia cells' appetite for fat seems to be formidable," Taegtmeyer said. "More importantly, fat oxidation seems to promote leukemia cell survival. Conversely, shutting off fat oxidation makes the cells vulnerable to self-destruction. If these initial results hold up, inhibitors of fat oxidation may become a new way to treat leukemia patients."

In normal cells, the processing of fatty acids in the cell's power-generating mitochondria leads to production of ATP, a molecule that serves as the major source of energy for the cell. The researchers showed that fatty acid oxidation in leukemia cell mitochondria drives cellular oxygen consumption and inhibits the activity of proteins that are vital to apoptosis, the programmed death of defective cells that begins in the mitochondria.

For energy generation, leukemia cells rely on glycolysis, the processing of a glucose molecule in the cellular cytoplasm that produces two molecules of ATP and two of pyruvate. Pyruvate, in turn, is converted to energy by the Krebs Cycle, a series of chemical reactions inside the mitochondria.

In a series of lab experiments, the researchers demonstrated that etomoxir, a drug used to treat heart failure, inhibits the growth of leukemia cells in culture in a dose-dependent manner. They also found that etomoxir sensitizes leukemia cells to drugs that cause apoptosis. The fatty acid synthase/lipase inhibitor orlistat also sensitized leukemia cells to programmed cell death.

Etomoxir treats heart failure by switching the heart's energy supply from fatty acids to pyruvate, which is more efficiently converted to energy by the mitochondria.

Mouse model experiments showed that combining etomoxir with the apoptosis-inducing drug ABT-737 or with cytarabine, a frontline drug for acute myeloid leukemia, reduced the leukemia burden and increased median survival time by 33 percent and 67 percent respectively compared to control group mice.

Additionally, etomoxir was found to decrease the number of quiescent leukemia progenitor cells in half of blood samples taken from acute myeloid leukemia patients. These quiescent cells are important, the researchers note, because they are capable of initiating leukemia and are highly resistant to traditional chemotherapy.

"Our findings suggest that mitochondrial function and resistance to apoptosis in leukemia cells are intimately linked with the entry of fatty acids into mitochondria," said first author Ismael Samudio, M.D., a fellow in Stem Cell Transplantation and Cellular Therapy. "For many years it has been apparent that leukemia cells are addicted to glucose for the generation of cellular energy (ATP). Now our results suggest that leukemia cells are addicted to fatty acids for the function of the Krebs cycle and the prevention of cell death."


'/>"/>

Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

Related medicine news :

1. Hair Cloning Not Yet Recommended by Researchers Who Developed the Technique
2. Researchers develop new tool for gene delivery
3. Researchers at Meharry Medical College Find Green Tea Extract Showing Promise for Treatment of Uterine Fibroids
4. Researchers welcome new multiple sclerosis drug
5. Barrow researchers receive more than $2 million in NIH grants for nicotine studies
6. Researchers discover method to objectively identify PTSD
7. Researchers find a treatment for deadly brain tumor
8. Researchers find new insights into inherited retinal disease
9. Pitt researchers raise concern over frequency of surveillance colonoscopy
10. Stress triggers tumor formation, Yale researchers find
11. Johns Hopkins researchers say vaccine appears to mop up leukemia cells Gleevec leaves behind
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:7/23/2017)... Opelousas, LA (PRWEB) , ... July 23, 2017 ... ... providers to interact, thus improving communication, safety and patient-provider relationships. New tools are ... according to results of the 19th Annual Health Care’s Most Wired® survey, released ...
(Date:7/23/2017)... ... July 23, 2017 , ... ... Florida Pain Relief Group – Melbourne, a practice owned by Physician Partners of ... interventional pain management, Dr. Stern also is certified in pediatrics, emergency medicine and ...
(Date:7/23/2017)... ... ... Viora Ltd., a leading medical aesthetics solutions manufacturer, is ... United States Patent and Trademark Office. The patent applies to treatments with Viora’s ... mechanisms to further increase the efficacy and safety of final treatment results for ...
(Date:7/22/2017)... , ... July 22, 2017 , ... ... year with the majority of patients not requiring pain medication after three months ... Sports Medicine’s Annual Meeting today in Toronto, Ontario, Canada found that those ...
(Date:7/21/2017)... PITTSBURGH, PA (PRWEB) , ... July 21, 2017 , ... ... I use a lot of pleural catheters available on the market," said an inventor ... level of comfort and safety for the patient." , He developed the patent-pending PLEURAL ...
Breaking Medicine News(10 mins):
(Date:7/11/2017)... , July 11, 2017  The global market for ... of approximately $394.1 million in 2016.  Although in early ... solid growth, in particular as a result of the ... and the recent introduction of a significant number of ... less-invasive testing of tumor biomarkers to guide treatment decisions. ...
(Date:7/11/2017)... 11, 2017  Dr. Echenberg, founder of Echenberg Institute, is announcing a ... who suffer from painful intercourse and other painful pelvic pain conditions such ... to menopause. ... LLC ... Sarasota, Florida -based start-up company, VuVatech LLC, fills a void ...
(Date:7/10/2017)... , July 10, 2017  US medical equipment and ... 2021, according to Medical Equipment & Supplies: ... Freedonia Focus Reports. Continued increases in demand for medical ... of the population and supported by gains in disposable ... and supplies. New product introductions will also drive sales ...
Breaking Medicine Technology: