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:10/13/2017)... ... October 13, 2017 , ... “America On The Brink”: the ... “America On The Brink” is the creation of published author, William Nowers. Captain ... As a WWII veteran, he spent thirty years in the Navy. Following his ...
(Date:10/12/2017)... ... ... Planet Fitness, one of the largest and fastest growing franchisors and operators ... location in Covington, LA at 401 N. U.S. Highway 190, in January of 2018. ... in the Holiday Square shopping center. Its location allows it to serve both Covington ...
(Date:10/12/2017)... ... October 12, 2017 , ... The American College of Medical Informatics (ACMI) ... FACMI, during the Opening Session of AMIA’s Annual Symposium in Washington, D.C. AMIA’s ... Morris F. Collen, a pioneer in the field of medical informatics, this prestigious award ...
(Date:10/12/2017)... ... October 12, 2017 , ... Dr. Parsa ... contributed a medical article to the newly revamped Cosmetic Town journal ... the hair transplant procedure known as Follicular Unit Extraction (FUE). , ...
(Date:10/12/2017)... ... October 12, 2017 , ... On Saturday, October 21, the ... – Miles by Moonlight to raise money for the American Heart Association Heart Walk. ... , Teams will work together to keep their treadmills moving for 5 hours. Treadmills ...
Breaking Medicine News(10 mins):
(Date:9/25/2017)... 25, 2017   Montrium , an industry ... today—from the IQPC Trial Master Files & Inspection ... that EastHORN Clinical Services has selected eTMF ... TMF management. EastHORN, a leading European contract research ... increase transparency to enable greater collaboration with sponsors, ...
(Date:9/23/2017)... Janssen Biotech, Inc. (Janssen) announced today that ... U.S. Food and Drug Administration (FDA) for the Biologics ... treatment of moderately to severely active rheumatoid arthritis (RA). ... needed to further evaluate the safety of sirukumab in ... "We are disappointed ...
(Date:9/22/2017)... SAN DIEGO , Sept. 22, 2017 ... ll medical device is now successfully helping those with ... Union. Fibromyalgia diagnosed Amanda in ... getting dressed and washing my hair, experiencing no sleep ... body in painful spasm… I cannot recommend [the AVACEN ...
Breaking Medicine Technology: