Multiple Myeloma Survival Associated with Enzyme Levels
By LabMedica International staff writers Posted on 21 Dec 2017 |
Image: Bone marrow biopsy of a patient with multiple myeloma, showing diffuse infiltration by neoplastic plasma cells, which can be recognized by the eccentric nucleus and perinuclear halo (Photo courtesy of Dr. Michael G. Bayerl).
Multiple myeloma (MM) is the second most common blood cancer in the USA and 30% to 50% of multiple myeloma patients have extra copies of the gene that encodes the enzyme Adenosine Deaminase, RNA Specific (ADAR1).
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.
Scientists at the University of California San Diego School of Medicine (La Jolla, CA, USA) obtained bone marrow samples from MM patient and normal age-matched controls. Peripheral blood (PB) or bone marrow (BM) samples were processed by Ficoll density centrifugation and viable total mononuclear cells (MNC) were collected for further analyses and stored in liquid nitrogen. RNA editing site-specific quantitative real time polymerase chain reaction (RESSq-PCR) assay primer design was carried out for specific cancer and stem cell-associated loci. The team performed several other molecular procedures to confirm their results.
The scientists analyzed a database of nearly 800 multiple myeloma patient samples, and 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% of patients with low ADAR1 levels survived longer than two years after their initial diagnosis, fewer than 70% of patients with high ADAR1 levels were alive after the same period of time.
The 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.
Catriona H. M. Jamieson, MD, PhD, professor of medicine and senior author of the study, said, “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. 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.” The study was published on December 4, 2017, in the journal Nature Communications.
Related Links:
University of California San Diego School of Medicine
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.
Scientists at the University of California San Diego School of Medicine (La Jolla, CA, USA) obtained bone marrow samples from MM patient and normal age-matched controls. Peripheral blood (PB) or bone marrow (BM) samples were processed by Ficoll density centrifugation and viable total mononuclear cells (MNC) were collected for further analyses and stored in liquid nitrogen. RNA editing site-specific quantitative real time polymerase chain reaction (RESSq-PCR) assay primer design was carried out for specific cancer and stem cell-associated loci. The team performed several other molecular procedures to confirm their results.
The scientists analyzed a database of nearly 800 multiple myeloma patient samples, and 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% of patients with low ADAR1 levels survived longer than two years after their initial diagnosis, fewer than 70% of patients with high ADAR1 levels were alive after the same period of time.
The 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.
Catriona H. M. Jamieson, MD, PhD, professor of medicine and senior author of the study, said, “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. 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.” The study was published on December 4, 2017, in the journal Nature Communications.
Related Links:
University of California San Diego School of Medicine
Latest Molecular Diagnostics News
- Novel Biomarkers to Improve Diagnosis of Renal Cell Carcinoma Subtypes
- RNA-Powered Molecular Test to Help Combat Early-Age Onset Colorectal Cancer
- Advanced Blood Test to Spot Alzheimer's Before Progression to Dementia
- Multi-Omic Noninvasive Urine-Based DNA Test to Improve Bladder Cancer Detection
- First of Its Kind NGS Assay for Precise Detection of BCR::ABL1 Fusion Gene to Enable Personalized Leukemia Treatment
- Urine Test to Revolutionize Lyme Disease Testing
- Simple Blood Test Could Enable First Quantitative Assessments for Future Cerebrovascular Disease
- New Genetic Testing Procedure Combined With Ultrasound Detects High Cardiovascular Risk
- Blood Samples Enhance B-Cell Lymphoma Diagnostics and Prognosis
- Blood Test Predicts Knee Osteoarthritis Eight Years Before Signs Appears On X-Rays
- Blood Test Accurately Predicts Lung Cancer Risk and Reduces Need for Scans
- Unique Autoantibody Signature to Help Diagnose Multiple Sclerosis Years before Symptom Onset
- Blood Test Could Detect HPV-Associated Cancers 10 Years before Clinical Diagnosis
- Low-Cost Point-Of-Care Diagnostic to Expand Access to STI Testing
- 18-Gene Urine Test for Prostate Cancer to Help Avoid Unnecessary Biopsies
- Urine-Based Test Detects Head and Neck Cancer