Breaking News
October 16, 2018 - Researchers demonstrate integrated technique to control production of cell therapeutics
October 16, 2018 - Breast tomosynthesis detects 34% more tumors than traditional mammography
October 16, 2018 - Rhode Island Hospital, Brown receive $800,000 grant to keep up fight against opioid epidemic
October 16, 2018 - Trevena Announces Oliceridine FDA Advisory Committee Meeting Outcome
October 16, 2018 - Study reveals early warning signs of heart problems in patients with newly diagnosed lupus
October 16, 2018 - Connecting the dots of Alzheimer’s disease
October 16, 2018 - New publication offers evidence-based content for global breast imaging medical community
October 16, 2018 - ‘EinsteinVision’ that improves hand-eye coordination of surgeons introduced at Harefield Hospital
October 16, 2018 - WRAIR clinical study evaluates safety and immunogenicity of Marburg vaccine
October 16, 2018 - Ketamine can be considered as alternative to opioids for short-term pain control in ED
October 16, 2018 - Endurance exercise training beneficially alters gut microbiota composition
October 15, 2018 - FDA Approves Yutiq (fluocinolone acetonide intravitreal implant) for Chronic Non-Infectious Posterior Segment Uveitis
October 15, 2018 - Birthing Options for Full-Term Pregnancy
October 15, 2018 - Stressed, toxic, zombie cells seen for first time in Alzheimer’s
October 15, 2018 - Concussion researchers study head motion in high school football hits | News Center
October 15, 2018 - Neuropsychiatric symptoms related to earliest stages of Alzheimer’s brain pathology
October 15, 2018 - Neck collar device may help protect the brain of female high school soccer players
October 15, 2018 - Research reveals how the inner ear processes speech
October 15, 2018 - Many parents still skeptical about safety and effectiveness of flu shot, survey finds
October 15, 2018 - Payer Policies May Discourage Non-Pharma Tx for Low Back Pain
October 15, 2018 - Exercise may delay cognitive decline in people with rare Alzheimer’s disease
October 15, 2018 - Researchers modify CRISPR to reorganize genome | News Center
October 15, 2018 - Innovative brain tumor operation set to tailor to patients’ needs
October 15, 2018 - Findings offer new insight into early changes that occur during AD pathology
October 15, 2018 - Neurons regulating reproductive hormone release have different activity in epileptic mice
October 15, 2018 - More parents are concerned about taking babies swimming in public pools
October 15, 2018 - Health Tip: Know the Risk Factors for Lower Back Pain
October 15, 2018 - Study shows cigarillo flavors enhanced by high-intensity sweeteners
October 15, 2018 - Study traces hospital-acquired bloodstream infections to patients’ own bodies | News Center
October 15, 2018 - Abnormal vision in childhood can affect development of brain areas responsible for attention
October 15, 2018 - Study highlights need for increased support for alcohol-related liver disease patients
October 15, 2018 - Color-changing contact lens could help doctors to monitor eye disease medications
October 15, 2018 - Tobacco heating products cause less staining to teeth than conventional cigarettes
October 15, 2018 - Young adults who are obese can expect to lose up to 10 years in life expectancy
October 15, 2018 - Scientists uncover how proteins meet on the cell membrane
October 15, 2018 - Affordable housing with supportive social services for senior citizens can reduce hospital use
October 15, 2018 - Schiller Easy Pulse Saves Lives
October 15, 2018 - The latest ECG device from Schiller
October 15, 2018 - Following a Tissue Sample
October 15, 2018 - Prisoners need drug and alcohol treatments but AA programs aren’t the answer
October 15, 2018 - Andrea Califano and Jordan Orange Elected to National Academy of Medicine
October 15, 2018 - The impending risk of African Swine Fever Virus
October 15, 2018 - Breastfeeding reduces the number of antibiotic-resistant bacteria in infant gut
October 15, 2018 - Researchers develop comprehensive molecular atlas of postnatal mouse heart development
October 15, 2018 - ObsEva SA Presents Clinical Data from Phase III IMPLANT 2 Trial of Nolasiban in IVF at the American Society of Reproductive Medicine (ASRM) Annual Meeting
October 15, 2018 - Engineering teratoma-derived fibroblasts to enhance osteogenesis
October 15, 2018 - Lab study shows effectiveness of potential therapy for treatment-resistant hypothyroidism
October 15, 2018 - JCU study firms up association between diet and depression
October 15, 2018 - Researchers to study the use of CRISPR on human liver on-a-chip platform
October 15, 2018 - Sub-concussive impacts not associated with decline in neurocognitive function
October 15, 2018 - Researchers find potential treatment to halt premature labor and birth
October 15, 2018 - As U.S. suicides rates rise, Hispanics show relative immunity
October 15, 2018 - FDA Issues a Complete Response Letter to Acacia Pharma for Barhemsys
October 15, 2018 - Photoactive bacteria bait may help in fight against MRSA infections
October 15, 2018 - Increasing vigorous exercise reduces risk factors of type 2 diabetes, cardiovascular disease in children
October 15, 2018 - First-of-its-kind study to test a personalized vaccine in cancer patient
October 15, 2018 - Extension trial assesses benefit of switching from flash monitoring to RT-CGM for hypoglycemia
October 15, 2018 - Half of parents say young children are afraid of doctor’s visits
October 15, 2018 - Study shows how fingerprint-based drug screening works on the living and deceased
October 15, 2018 - Study reveals potential to monitor progression of Alzheimer’s disease by measuring brain antioxidant levels
October 15, 2018 - FDA Approves Xarelto to Reduce the Risk of Major Cardiovascular Events in Patients with Chronic Coronary Artery Disease (CAD) or Peripheral Artery Disease (PAD)
October 15, 2018 - Promising new therapeutic approach against Ebola virus identified
October 15, 2018 - Study unravels how cancer stem cells use normal genes in abnormal ways
October 15, 2018 - Healthcare systems fail to deliver at affordable prices finds report
October 15, 2018 - Intensive BP Therapy in Diabetes May Lower Risk for CV Events
October 15, 2018 - Muscle relaxants increase risk of respiratory complications
October 15, 2018 - Female birds become more promiscuous after hatchings fail in the first breeding attempt
October 15, 2018 - Humans occupied Madagascar thousands of years later than previously thought
October 15, 2018 - Is Kidney Dialysis Always Needed When Septic Shock Strikes?
October 15, 2018 - Study shows invasive lung cancer surgery can lead to long-term opioid use
October 15, 2018 - Sugar, a “sweet” tool to understand brain injuries
October 14, 2018 - King’s commemorates activities and research on World Arthritis Day
October 14, 2018 - Humana and VFW NY team up on Stop 22 initiative to increase awareness of veterans committing suicide
October 14, 2018 - Water fluoridation contributes to urinary fluoride levels in pregnant women in Canada
October 14, 2018 - Study of children in Romanian orphanages tells cautionary tale about family separation
October 14, 2018 - Previous Endologix AFX Safety Notice classified by FDA as Class I recall
October 14, 2018 - Legal scholars sound alarm on academies’ report about returning research results to participants
October 14, 2018 - UNIST selects six extraordinary scholars to be induced as ‘Rising-star Distinguished Professor’
October 14, 2018 - Scientists find new way to help asthmatics breathe more easily
October 14, 2018 - New ‘gag rule’ may adversely impact health care of pregnant women
High ADAR1 enzyme levels correlate with reduced survival rates in multiple myeloma

High ADAR1 enzyme levels correlate with reduced survival rates in multiple myeloma

image_pdfDownload PDFimage_print

Multiple myeloma is the second most common blood cancer in the United States. Thirty to 50 percent of multiple myeloma patients have extra copies of the gene that encodes the enzyme ADAR1. Using a database of multiple myeloma patient samples and information, researchers at University of California San Diego School of Medicine found that high ADAR1 levels correlate with reduced survival rates. They also determined that blocking the enzyme reduces multiple myeloma regeneration in experimental models derived from patient cancer cells.

The study, published December 4 in Nature Communications, also suggests that a class of commercially available drugs could be used to dampen ADAR1 activity, and ultimately prevent progression or relapse in multiple myeloma.

“Despite new therapies, it’s virtually inevitable that a patient with multiple myeloma will experience relapse of the disease at some point,” said senior author Catriona Jamieson, MD, PhD, professor of medicine, Koman Family Presidential Endowed Chair in Cancer Research and chief of the Division of Regenerative Medicine at UC San Diego School of Medicine. “That’s why it’s exciting that this discovery may allow us to detect the disease earlier, and address the root cause.”

The enzyme at the center of this study, ADAR1, is normally expressed during fetal development to help blood cells form. ADAR1 edits the sequence of RNA, a type of genetic material related to DNA. By swapping out just one RNA building block for another, ADAR1 alters the carefully orchestrated system cells use to control which genes are turned on or off at which times.

ADAR1 is known to promote cancer progression and resistance to therapy. In previous studies, Jamieson’s team described ADAR1’s contributions to leukemia. The enzyme’s RNA-editing activity boosts cancer stem cells — a special population of cells that can self-renew, giving rise to cancer, increasing recurrence and allowing some cancers to resist treatment.

In their current study, the team investigated ADAR1’s role in multiple myeloma. Analyzing a database of nearly 800 multiple myeloma patient samples, they discovered that 162 patients with low ADAR1 levels in their tumor cells survived significantly longer over a three-year period compared to 159 patients with high ADAR1 levels. While more than 90 percent of patients with low ADAR1 levels survived longer than two years after their initial diagnosis, fewer than 70 percent of patients with high ADAR1 levels were alive after the same period of time.

To unravel exactly how ADAR1 is connected to disease severity at a molecular level, the researchers transferred multiple myeloma patient tissue to mice, creating what’s known as a xenograft or “humanized” model.

“This is a difficult disease to model in animals — there isn’t a single gene we can manipulate to mimic multiple myeloma,” said co-senior author Leslie A. Crews, PhD, assistant professor at UC San Diego School of Medicine. “This study is important, in part because we now have a new xenograft model that will for the first time allow us to apply new biomarkers to better predict disease progression and test new therapeutics.”

Using their new model, Jamieson, Crews and team found that two events converge to activate ADAR1 in multiple myeloma — a genetic abnormality and inflammatory cues from the surrounding bone marrow tissue. Together, these signals activate ADAR1, which edits specific RNA in a way that stabilizes a gene that can make cancer stem cells more aggressive.

They also found that silencing the ADAR1 gene in the xenograft model reduced multiple myeloma regeneration. Five to 10-fold fewer tumor cells were able to self-renew in mice lacking ADAR1, suggesting a new therapeutic target.

Clinical trials that specifically test ADAR1-targeted therapeutics for their safety and efficacy against multiple myeloma are still necessary before this approach could become available to patients. To advance their initial findings, Jamieson and Crews are exploring ways to leverage ADAR1 to detect multiple myeloma progression as early as possible. They are also testing inhibitors of JAK2, a molecule that influences ADAR1 activity, for their ability to eliminate cancer stem cells in multiple myeloma models. Several JAK2 inhibitors have already been approved by the FDA or are currently in clinical trials for the treatment of other cancers.

“Several major advances in recent years have been good news for multiple myeloma patients, but those new drugs only target terminally differentiated cancer cells and thus can only reduce the bulk of the tumor,” said Jamieson, who is also deputy director of the Sanford Stem Cell Clinical Center, director of the CIRM Alpha Stem Cell Clinic at UC San Diego and director of stem cell research at Moores Cancer Center at UC San Diego Health. “They don’t get to the root cause of disease development, progression and relapse — cancer stem cells — the way inhibiting ADAR1 does. I like to call our approach ‘precision regenerative medicine.”

Source:

http://ucsdnews.ucsd.edu/pressrelease/in_multiple_myeloma_high_levels_of_enzyme_adar1_are_associated_with_reduced

Tagged with:

About author

Related Articles