Navigation Links
Enzyme accelerates malignant stem cell cloning in chronic myeloid leukemia
Date:12/24/2012

An international team, headed by researchers at the University of California, San Diego School of Medicine, has identified a key enzyme in the reprogramming process that promotes malignant stem cell cloning and the growth of chronic myeloid leukemia (CML), a cancer of the blood and marrow that experts say is increasing in prevalence.

The findings are published in the Dec. 24 online early edition of the Proceedings of the National Academy of Sciences (PNAS).

Despite the emergence of new therapies, such as tyrosine kinase inhibitors, CML and other leukemias remain problematic because some cancer stem cells avoid destruction and eventually regenerate themselves, a stem cell process known as self-renewal that can result in a return and spread (metastasis) of the disease.

In the PNAS paper, principal investigator Catriona H. M. Jamieson, MD, PhD, associate professor of medicine at UC San Diego, with colleagues in the United States, Canada and Italy, report that inflammation long associated with the development of cancer boosts activity of an enzyme called adenosine deaminase or ADAR1.

Expressed during embryogenesis to help blood cell development, ADAR1 subsequently turns off and is triggered by viral infections where it protects normal hematopoietic stem cells from attack. In leukemia stem cells, however, overexpression of ADAR1 enhances the missplicing of RNA, which leads to greater self-renewal and therapeutic resistance of malignant stem cells.

The findings build upon previous studies by Jamieson and others that elucidate the effects of RNA missplicing and instability. "People normally think about DNA instability in cancer, but in this case, it's how the RNA is edited by enzymes that really matters in terms of cancer stem cell generation and resistance to conventional therapy."

The described RNA editing process, which occurs in the context of human and other primate specific sequences, also underscores the importance of addressing inflammation as "an essential driver of cancer relapse and therapeutic resistance," Jamieson said. It also presents a new target for future therapies.

"ADAR1 is an enzyme that we may be able to specifically target with a small molecule inhibitor, an approach we have already used effectively with other inhibitors," said Jamieson. "If we can block the capacity of leukemia stem cells to use ADAR1, if we can knock down that pathway, maybe we can put stem cells back on the right track and stop malignant cloning."

CML is a cancer initiated by a mutant gene called BCR-ABL in blood forming stem cells that leads to an expansion of white blood cells and their precursors. It is typically slow-growing and often not diagnosed until its later stages when there can be a sudden, dramatic increase in malignant cells, known as blast crisis. Median age of diagnosis is 66 years; incidence of the disease increases with age. Despite tremendous advances in BCR-ABL tyrosine kinase inhibitor therapies, the majority of patients relapse if therapy is discontinued, in part as a result of dormant cancer stem cell resistance. This work suggests a novel mechanism for overcoming cancer stem cell resistance to therapy that may prevent relapse and progression.

The estimated prevalence of CML in the United States is 70,000 persons with the disease, projected to steadily increase to approximately 181,000 by 2050. CML is initiated by the mutant BCR-ABL gene, but scientists have not yet identified the cause of the mutation.


'/>"/>

Contact: Scott LaFee
slafee@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert  

Related medicine news :

1. Fast-acting enzymes with 2 fingers: Protein structurally and dynamically explained
2. Mayo Clinic researchers identify enzyme linked to prostate cancer
3. Enzymes may point toward better therapies for prediabetes
4. Synchrotron gives insight into green energy enzymes
5. Enzyme explains angina in diabetics
6. Gateway enzyme for chemicals from catnip to cancer drug
7. Structure of enzyme unravelled providing basis for more accurate design of chemotherapeutic drugs
8. Mayo Clinic researchers identify new enzyme to fight Alzheimers disease
9. Compounds activate key cancer enzyme to interfere with tumor formation
10. Enzymes implicated in disease processes attack one another instead of harming body proteins
11. Clemson researchers collect and reuse enzymes while maintaining bioactivity
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Enzyme accelerates malignant stem cell cloning in chronic myeloid leukemia
(Date:12/7/2016)... TX (PRWEB) , ... December 07, 2016 , ... ... 2016 Top 20 Marketing Campaign Winner in the Folio: Marketing Awards competition. Live ... recognize the year’s best in pioneering, inventive, and ultimately successful projects undertaken by ...
(Date:12/7/2016)... City, CA (PRWEB) , ... December 07, 2016 , ... ... during the holidays and winter seasons. One major study analyzing heart attacks among ... compared to August of a given year. We would all agree of course–no time ...
(Date:12/7/2016)... ... December 07, 2016 , ... "ProBrand Flip allows FCPX ... media," said Christina Austin - CEO of Pixel Film Studios. , ProBrand Flip includes ... use drop zones. Editors can select from a variety of flip book animations. In ...
(Date:12/7/2016)... CINCINNATI, Ohio (PRWEB) , ... December 07, 2016 ... ... winner in the 2016 BOC Business Brilliance Awards under the Best New Product ... inception and results achieved through user experience. , BOC Global Events & Training ...
(Date:12/7/2016)... ... December 07, 2016 , ... ... its newest portable bioelectronic medicine device WellnessPro Plus for consumers and healthcare ... enhances the WellnessPro platform by expanding the treatment modalities available in a ...
Breaking Medicine News(10 mins):
(Date:12/6/2016)... , Dec. 6, 2016  Nearly 30 million people ... from the epidemic of diabetes. 1 However, nearly ... elevated glucose levels (hyperglycemia) and significant glucose variability. 2 ... complications, including cardiovascular events. If left untreated, hyperglycemia can ... eye disease or blindness. 3 As ...
(Date:12/6/2016)... With opioids commonly used for pain management for workplace ... that has led to nationwide fatalities. The synthetic opioid ... than heroin or morphine, resulting in likelihood of addiction, abuse or ... , , ... operations, Behavioral Health for HMC HealthWorks, explained the opioid drug is ...
(Date:12/6/2016)... , Dec. 6, 2016  Blueprint Medicines Corporation ... and developing targeted kinase medicines for patients with genomically ... underwritten public offering of $125,000,000 million in shares of ... grant the underwriters a 30-day option to purchase up ... its common stock in connection with the public offering. ...
Breaking Medicine Technology: