NUS study: RNA defects linked to multiple myeloma progression in high risk patients

October 31, 2018

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."
-end-
The study was published in scientific journal, Blood, in September 2018.

National University of Singapore

Related Multiple Myeloma Articles from Brightsurf:

Penn Study supports use of radiation before CAR therapy for multiple myeloma
Administering radiation therapy to multiple myeloma patients waiting for CAR T cells to be manufactured was found to be safe and undisruptive to CAR T therapy.

New multiple myeloma therapy shows promise in preclinical study
A new alpha-radioimmunotherapy, 212Pb-anti-CD38, has proven effective in preventing tumor growth and increasing survival in multiple myeloma tumor-bearing mice, according to new research published in the July issue of The Journal of Nuclear Medicine.

A safer cell therapy harnesses patient T cells to fight multiple myeloma
A treatment for multiple myeloma that harnesses the body's cancer-fighting T cells was safe in humans and showed preliminary signs of effectiveness, according to a clinical trial involving 23 patients with relapsed or treatment-resistant disease.

Colorado tool, My-DST, may pick best multiple myeloma treatment
Response of liquid biopsies to approved drugs can help show resistance, predict response.

Case study: Treating COVID-19 in a patient with multiple myeloma
A case study of a patient in Wuhan, China, suggests that the immunosuppressant tocilizumab may be an effective COVID-19 treatment for very ill patients who also have multiple myeloma and other blood cancers.

New drug could reverse treatment resistance in advanced multiple myeloma
Researchers at the VU University Medical Center in the Netherlands have tested a new drug in patient samples and mice with multiple myeloma and discovered that it was effective even in advanced disease -- a point when many patients currently run out of options.

Single gene cluster loss may contribute to initiation/progression of multiple myeloma
The loss of one copy of the miR15a/miR16-1 gene cluster promoted initiation and progression of multiple myeloma in mice.

New CAR-T target yields promising results for multiple myeloma
In research published today in the journal Nature Communications, Utah-based scientists describe a novel way to treat cancers using chimeric antigen receptor (CAR) T cell therapy.

BCMA-targeted immunotherapy can lead to durable responses in multiple myeloma
An experimental, off-the-shelf immunotherapy that combines a targeted antibody and chemotherapy can lead to potentially durable responses in multiple myeloma patients whose disease has relapsed or is resistant to other standard therapies.

Study finds racial disparities in treatment of multiple myeloma patients
Among patients with multiple myeloma, African-Americans and Hispanics start treatment with a novel therapy significantly later than white patients, according to a new study published today in Blood Advances.

Read More: Multiple Myeloma News and Multiple Myeloma Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.