Breaking News
December 11, 2018 - Cartilage tissue engineering brings good news for patients with cartilage defects
December 11, 2018 - Novel 3D printing workflow helps predict leaky heart valves
December 11, 2018 - Are caries linked to political regime?
December 11, 2018 - Leader in Diabetes Clinical Trials Wins Naomi Berrie Award
December 11, 2018 - Scientists discover cellular mechanism that triggers pneumonia in humans
December 11, 2018 - Increasing mental health problems related to drug use in over 55’s
December 11, 2018 - High-intensity interval exercise could help combat cognitive dysfunction in obese people
December 11, 2018 - Annual flu shot can save lives of heart failure patients
December 11, 2018 - Researchers compare health outcomes for VA and non-VA hospitals
December 11, 2018 - Recommendations Developed for Psoriatic Arthritis Treatment
December 11, 2018 - Genetic analysis links obesity with diabetes, coronary artery disease
December 11, 2018 - Study shows that having genetic information can affect how the body responds
December 11, 2018 - UNAIDS Report: 9 Million Are Likely HIV Positive And Don't Know It
December 11, 2018 - Lund University researchers succeed in obtaining dendritic cells by direct reprogramming
December 11, 2018 - Breast tumors recruit bone marrow cells to boost their growth, study reveals
December 11, 2018 - Updated breast cancer screening guideline highlights importance of shared decision-making
December 11, 2018 - EHR-related stress associated with physician burnout
December 11, 2018 - AHA: 12-Year-Old Heart Defect Survivor Inspires NFL Player’s Foundation
December 11, 2018 - Breast cancer patients who take heart drug with trastuzumab have less heart damage
December 11, 2018 - Providing aid to those humans – and animals – affected by the California fires
December 11, 2018 - Even without proof, CBD is finding a niche as a cure-all
December 11, 2018 - Drawing leads to better memory than writing
December 11, 2018 - Researchers report novel findings on plant hormone
December 10, 2018 - A Tale of Two Labels
December 10, 2018 - Triple combination cancer immunotherapy improves outcomes in preclinical melanoma model
December 10, 2018 - A 14-year-old explains what it’s like to get a new heart
December 10, 2018 - Team Players Honored with 2018 Baton Awards
December 10, 2018 - Global report highlights how the changing world is affecting children’s physical activity levels
December 10, 2018 - Genes play a role in physical activity and sleep
December 10, 2018 - DDT in Alaskan fish shown to increase risk of cancer
December 10, 2018 - Laws to curb use of cell phones have greatly reduced fatalities for motorcyclists
December 10, 2018 - Argenx Provides Detailed Data from Phase 2 Clinical Trial of Efgartigimod in Immune Thrombocytopenia and Phase 1/2 Clinical Trial of Cusatuzumab in Acute Myeloid Leukemia
December 10, 2018 - University of Maryland doctors treat first breast cancer patients with GammaPod radiotherapy
December 10, 2018 - The heartbeat seat: Demoing new well-being technologies in a car
December 10, 2018 - Leading Cancer Researcher to Direct Herbert Irving Comprehensive Cancer Center
December 10, 2018 - Researchers explore how glial cells develop in the brain from neural precursor cells
December 10, 2018 - Study compares pain-related diagnoses in First Nations and non-First Nations children, youth
December 10, 2018 - Experts address sleep disorders following traumatic brain injury
December 10, 2018 - Scientists find answers to how cancer spreads
December 10, 2018 - Study explores why older people read more slowly
December 10, 2018 - Smart life-collar could save lives of young children
December 10, 2018 - Asbestos found in most NHS hospitals finds BBC inquiry
December 10, 2018 - Researchers use new technique to probe hydrogen bonds
December 10, 2018 - Music improves social communication in autistic children
December 10, 2018 - Some Brain Tumors May Respond to Immunotherapy, New Study Suggests
December 10, 2018 - Banning junk food ads to combat childhood obesity
December 10, 2018 - Skin Autofluorescence Predicts T2DM, Heart Disease, Mortality
December 10, 2018 - Largest autism sequencing study to date yields 102 genes associated with ASD
December 10, 2018 - Statins associated with low risk of side effects
December 10, 2018 - Episodic memory tests help in predicting brain atrophy and Alzheimer’s disease
December 10, 2018 - Study explores how schools address adolescent self-harming practices
December 10, 2018 - Pregnancy in adolescence linked to increased risks of complications in young mothers
December 10, 2018 - Risk Analysis publishes special issue on communicating about Zika virus
December 10, 2018 - Botox May Help Prevent Post-Op A-Fib
December 10, 2018 - African-American mothers rate boys higher for ADHD
December 10, 2018 - Graphic warning labels cancel out cigarettes’ appeal to young people
December 10, 2018 - Australian researchers to study gas inhalational anaesthetic and likelihood of cancer return
December 10, 2018 - Individual neurons located within the brain have implications for psychiatric diseases
December 10, 2018 - Researchers improve bariatric surgery scoring system to extend prediction time for diabetic remission
December 10, 2018 - HPV type 16 or 18 associated with cervical cancer risk in young women
December 10, 2018 - Cervical cancer risk is higher in women with positive HPV, but no cellular abnormalities
December 10, 2018 - Combo therapy not needed if low RA disease activity achieved
December 10, 2018 - Novel therapeutic targets based on biology of aging show promise for Alzheimer’s disease
December 10, 2018 - UC San Diego professor receives NCI Outstanding Investigator Award for cancer research
December 10, 2018 - Study evaluates placental mesenchymal stem cell sheets for myocardial repair and regeneration
December 10, 2018 - Blueprint Medicines Announces Updated Results from Ongoing EXPLORER Clinical Trial of Avapritinib Demonstrating Broad Clinical Activity and Significant Symptom Reductions in Patients with Systemic Mastocytosis
December 10, 2018 - Study clarifies ApoE4’s role in dementia
December 10, 2018 - Eating disorders now a top priority with Australian Government
December 10, 2018 - Neuronal activity in the brain allows prediction of risky or safe decisions
December 10, 2018 - FDA Alerts Health Care Professionals and Patients Not to Use Drug Products Intended to be Sterile from Promise Pharmacy
December 10, 2018 - Improving dementia care and treatment saves thousands of pounds in care homes
December 10, 2018 - Heroin-assisted treatment can offer benefits, reduce harms
December 10, 2018 - People covered by Michigan’s expanded Medicaid program report improvements in health, finds study
December 10, 2018 - Hazelnuts improve micronutrient levels in older adults
December 9, 2018 - History of Partner Violence Tied to Menopause Symptoms
December 9, 2018 - Clean Up Safely After a Disaster|Natural Disasters and Severe Weather
December 9, 2018 - Drug wholesalers drove fentanyl’s deadly rise, report concludes
December 9, 2018 - Deprescribing could help manage polypharmacy in older adults
December 9, 2018 - Retraction of article “Joy of cooking too much” from journal
December 9, 2018 - FDA Warns of Rare Stroke Risk With MS Drug Lemtrada (Alemtuzumab)
RNA defects linked to multiple myeloma progression in high risk patients

RNA defects linked to multiple myeloma progression in high risk patients

image_pdfDownload PDFimage_print
This is a computer graphic of an RNA molecule. Credit: Richard Feldmann/Wikipedia

Multiple myeloma (MM) is the second most common type of blood cancer where cancer cells accumulate in the bone marrow, crowding out healthy blood cells. Studies on MM development have traditionally focused mostly on DNA abnormalities, but a team of researchers from the Cancer Institute of Singapore (CSI Singapore) at the National University of Singapore has uncovered an association between RNA abnormalities and MM progression. In particular, the team discovered that overexpression of ADAR1, a RNA-editing enzyme, and a modified gene caused by irregular RNA editing are key to MM progression and the development of resistance to current treatments.

Survival rates for MM patients have significantly improved over the years with multiple new drug discoveries for the disease. However, about 10 to 15 per cent continue to be classified as high risk patients with low survival rates even when treated with the available drugs, as they develop resistance to the drug treatments.

Research on MM in the last decade was mostly aimed at understanding how DNA abnormalities contribute to the development of MM. More recently, RNA abnormalities have also been found to be associated with different cancers such as gastric cancer and liver cancer. As such, the team at CSI Singapore embarked on the study to investigate the biological implications of RNA defects on the progression of MM, so as to better understand how drug resistance develop in high risk MM patients.

The team’s analysis revealed that that the MM RNA exists in an abnormally modified state, which consequently promotes MM progression in two ways. The first is an abnormally elevated level of ADAR1 expression in myeloma cancer cells. This overexpression of ADAR1 causes myeloma cancer cells to acquire stronger cancer properties. The second is the irregular RNA editing of NEIL1, a gene associated with lung carcinoma and colorectal cancer. NEIL1-edited myeloma cancer cells demonstrate a more cancerous nature where they lose the ability to repair DNA damage and show increased resistance to a standard MM drug. Collectively, patients with high ADAR1 expression and compromised NEIL1 function were found to be less responsive towards the available treatments for MM.

Tapping on the newly established understanding, the CSI Singapore team also identified a group of drugs, known as DSB-inducing agents, which can be used to inhibit NEIL-edited cells, opening the door for new, effective treatment options for high risk MM patients.

Professor Chng Wee Joo, Deputy Director and Senior Principal Investigator at CSI Singapore, who led the study, said, “Our study has shown that RNA defects is both clinically and biologically relevant in MM, and by exploring these RNA abnormalities further, we may unravel more novel insights on MM molecular pathogenesis. Each piece of new knowledge derived will be key in helping to complete the puzzle of MM biology, paving the way for the development of innovative therapies that can curb drug resistance and raise the survival rates of high risk MM patients.”


Explore further:
Multiple myeloma survival down with high ADAR1 RNA expression

More information:
Phaik Ju Teoh et al. Aberrant hyperediting of the myeloma transcriptome by ADAR1 confers oncogenicity and is a marker of poor prognosis, Blood (2018). DOI: 10.1182/blood-2018-02-832576

Journal reference:
Blood

Provided by:
National University of Singapore

Tagged with:

About author

Related Articles