Fusion Circular RNAs May Be Linked to Leukemia
|
By LabMedica International staff writers Posted on 12 Apr 2016 |
|
Image: A bone marrow aspirate smear showing precursor B-cell acute lymphoblastic leukemia cells. Chromosomal translocations and gene fusions are common in various types of leukemia (Photo courtesy of Wikimedia Commons).
The activity of noncoding circular RNAs has been linked to the development of leukemia and other cancers.
Chromosomal translocations result in the production of oncogenic fusion proteins that are involved in tumor formation. Whether such genomic alterations also affect noncoding RNAs is unclear, and their impact on circular RNAs (circRNAs) has not been rigorously examined.
Investigators at Beth Israel Deaconess Medical Center (Boston, MA, USA) reported in the March 31, 2016, online edition of the journal Cell that well-established cancer-associated chromosomal translocations gave rise to fusion circRNAs (f-circRNA) that were produced from transcribed exons of distinct genes affected by the translocations. F-circRNAs contributed to cellular transformation, promoted cell viability, and resistance upon therapy and had tumor-promoting properties in animal models.
As chromosomal translocations are common in various types of leukemia, the investigators examined acute promyelocytic leukemia cells, which often carry a translocation between the PML (Promyelocytic leukemia protein) and RAR-alpha (Retinoic acid receptor alpha) genes and acute myeloid leukemia cells, which can harbor a translocation between the MLL (Histone-lysine N-methyltransferase 2A) and AF9 (myeloid/lymphoid or mixed-lineage leukemia; translocated to, 3) genes.
They found abnormal fusion-circular RNAs (f-circRNAs), corresponding to different exons associated with the PML-RAR-alpha gene fusion as well as the MLL-AF9 gene fusion.
Experiments were conducted in a mouse leukemia model that focused on a specific f-circRNA (f-circM9) associated with the MLL-AF9 fusion gene. Results indicated that the activity of f-circM9 in conjunction with other cancer-promoting signals could trigger the disease.
"Cancer is essentially a disease of mutated or broken genes, so that motivated us to examine whether circular RNAs, like proteins, can be affected by these chromosomal breaks," said senior author Dr. Pier Paolo Pandolfi, professor of medicine at Beth Israel Deaconess Medical Center. "These results are particularly exciting because they suggest that drugs directed at fusion-circular RNAs could be a powerful strategy to pursue for future therapeutic development in cancer. Our work paves the way to discovering many more of these unusual RNAs and how they contribute to cancer, which could reveal new mechanisms and druggable pathways involved in tumor progression."
Related Links:
Beth Israel Deaconess Medical Center
Chromosomal translocations result in the production of oncogenic fusion proteins that are involved in tumor formation. Whether such genomic alterations also affect noncoding RNAs is unclear, and their impact on circular RNAs (circRNAs) has not been rigorously examined.
Investigators at Beth Israel Deaconess Medical Center (Boston, MA, USA) reported in the March 31, 2016, online edition of the journal Cell that well-established cancer-associated chromosomal translocations gave rise to fusion circRNAs (f-circRNA) that were produced from transcribed exons of distinct genes affected by the translocations. F-circRNAs contributed to cellular transformation, promoted cell viability, and resistance upon therapy and had tumor-promoting properties in animal models.
As chromosomal translocations are common in various types of leukemia, the investigators examined acute promyelocytic leukemia cells, which often carry a translocation between the PML (Promyelocytic leukemia protein) and RAR-alpha (Retinoic acid receptor alpha) genes and acute myeloid leukemia cells, which can harbor a translocation between the MLL (Histone-lysine N-methyltransferase 2A) and AF9 (myeloid/lymphoid or mixed-lineage leukemia; translocated to, 3) genes.
They found abnormal fusion-circular RNAs (f-circRNAs), corresponding to different exons associated with the PML-RAR-alpha gene fusion as well as the MLL-AF9 gene fusion.
Experiments were conducted in a mouse leukemia model that focused on a specific f-circRNA (f-circM9) associated with the MLL-AF9 fusion gene. Results indicated that the activity of f-circM9 in conjunction with other cancer-promoting signals could trigger the disease.
"Cancer is essentially a disease of mutated or broken genes, so that motivated us to examine whether circular RNAs, like proteins, can be affected by these chromosomal breaks," said senior author Dr. Pier Paolo Pandolfi, professor of medicine at Beth Israel Deaconess Medical Center. "These results are particularly exciting because they suggest that drugs directed at fusion-circular RNAs could be a powerful strategy to pursue for future therapeutic development in cancer. Our work paves the way to discovering many more of these unusual RNAs and how they contribute to cancer, which could reveal new mechanisms and druggable pathways involved in tumor progression."
Related Links:
Beth Israel Deaconess Medical Center
Platinum Member
COVID-19 Rapid Test
OSOM COVID-19 Antigen Rapid Test
Complement 3 (C3) Test
GPP-100 C3 Kit
Gold Member
ADAMTS-13 Protease Activity Test
ATS-13 Activity Assay
Latest BioResearch News
- Genome Analysis Predicts Likelihood of Neurodisability in Oxygen-Deprived Newborns
- Gene Panel Predicts Disease Progession for Patients with B-cell Lymphoma
- New Method Simplifies Preparation of Tumor Genomic DNA Libraries
- New Tool Developed for Diagnosis of Chronic HBV Infection
- Panel of Genetic Loci Accurately Predicts Risk of Developing Gout
- Disrupted TGFB Signaling Linked to Increased Cancer-Related Bacteria
- Gene Fusion Protein Proposed as Prostate Cancer Biomarker
- NIV Test to Diagnose and Monitor Vascular Complications in Diabetes
- Semen Exosome MicroRNA Proves Biomarker for Prostate Cancer
- Genetic Loci Link Plasma Lipid Levels to CVD Risk
- Newly Identified Gene Network Aids in Early Diagnosis of Autism Spectrum Disorder
- Link Confirmed between Living in Poverty and Developing Diseases
- Genomic Study Identifies Kidney Disease Loci in Type I Diabetes Patients
- Liquid Biopsy More Effective for Analyzing Tumor Drug Resistance Mutations
- New Liquid Biopsy Assay Reveals Host-Pathogen Interactions
- Method Developed for Enriching Trophoblast Population in Samples
Channels
Clinical Chemistry
view channel
3D Printed Point-Of-Care Mass Spectrometer Outperforms State-Of-The-Art Models
Mass spectrometry is a precise technique for identifying the chemical components of a sample and has significant potential for monitoring chronic illness health states, such as measuring hormone levels... Read more.jpg "Image: Reaching speeds up to 6,000 RPM, this centrifuge forms the basis for a new type of inexpensive, POC biomedical test (Photo courtesy of Duke University)")
POC Biomedical Test Spins Water Droplet Using Sound Waves for Cancer Detection
Exosomes, tiny cellular bioparticles carrying a specific set of proteins, lipids, and genetic materials, play a crucial role in cell communication and hold promise for non-invasive diagnostics.... Read more
Highly Reliable Cell-Based Assay Enables Accurate Diagnosis of Endocrine Diseases
The conventional methods for measuring free cortisol, the body's stress hormone, from blood or saliva are quite demanding and require sample processing. The most common method, therefore, involves collecting... Read more
Molecular Diagnostics
view channel
Game-Changing Blood Test for Stroke Detection Could Bring Life-Saving Care to Patients
Stroke is the primary cause of disability globally and ranks as the second leading cause of death. However, timely early intervention can prevent severe outcomes. Most strokes are ischemic, resulting from... Read more
Blood Proteins Could Warn of Cancer Seven Years before Diagnosis
Two studies have identified proteins in the blood that could potentially alert individuals to the presence of cancer more than seven years before the disease is clinically diagnosed. Researchers found... Read more (1)_1.jpg "Image: Ultrasound image of micro-histotripsy liberation of biomarkers in a tumor (Photo courtesy of Joy Wang and Pradyumna Kedarisetti)"){kind=small}
_1.jpg "Image: The innovative method to customize and strengthen DNA origami structure promises breakthroughs in medicine (Photo courtesy of Shutterstock)")
Hematology
view channel
Next Generation Instrument Screens for Hemoglobin Disorders in Newborns
Hemoglobinopathies, the most widespread inherited conditions globally, affect about 7% of the population as carriers, with 2.7% of newborns being born with these conditions. The spectrum of clinical manifestations... Read more
First 4-in-1 Nucleic Acid Test for Arbovirus Screening to Reduce Risk of Transfusion-Transmitted Infections
Arboviruses represent an emerging global health threat, exacerbated by climate change and increased international travel that is facilitating their spread across new regions. Chikungunya, dengue, West... Read more
POC Finger-Prick Blood Test Determines Risk of Neutropenic Sepsis in Patients Undergoing Chemotherapy
Neutropenia, a decrease in neutrophils (a type of white blood cell crucial for fighting infections), is a frequent side effect of certain cancer treatments. This condition elevates the risk of infections,... Read more
First Affordable and Rapid Test for Beta Thalassemia Demonstrates 99% Diagnostic Accuracy
Hemoglobin disorders rank as some of the most prevalent monogenic diseases globally. Among various hemoglobin disorders, beta thalassemia, a hereditary blood disorder, affects about 1.5% of the world's... Read moreImmunology
view channel.jpg "Image: The AI predictive model identifies the most potent cancer killing immune cells for use in immunotherapies (Photo courtesy of Shutterstock)")
AI Predicts Tumor-Killing Cells with High Accuracy
Cellular immunotherapy involves extracting immune cells from a patient's tumor, potentially enhancing their cancer-fighting capabilities through engineering, and then expanding and reintroducing them into the body.... Read more
Diagnostic Blood Test for Cellular Rejection after Organ Transplant Could Replace Surgical Biopsies
Transplanted organs constantly face the risk of being rejected by the recipient's immune system which differentiates self from non-self using T cells and B cells. T cells are commonly associated with acute... Read more
AI Tool Precisely Matches Cancer Drugs to Patients Using Information from Each Tumor Cell
Current strategies for matching cancer patients with specific treatments often depend on bulk sequencing of tumor DNA and RNA, which provides an average profile from all cells within a tumor sample.... Read more
Genetic Testing Combined With Personalized Drug Screening On Tumor Samples to Revolutionize Cancer Treatment
Cancer treatment typically adheres to a standard of care—established, statistically validated regimens that are effective for the majority of patients. However, the disease’s inherent variability means... Read moreMicrobiology
view channel
Integrated Solution Ushers New Era of Automated Tuberculosis Testing
Tuberculosis (TB) is responsible for 1.3 million deaths every year, positioning it as one of the top killers globally due to a single infectious agent. In 2022, around 10.6 million people were diagnosed... Read more
Automated Sepsis Test System Enables Rapid Diagnosis for Patients with Severe Bloodstream Infections
Sepsis affects up to 50 million people globally each year, with bacteraemia, formerly known as blood poisoning, being a major cause. In the United States alone, approximately two million individuals are... Read more
Enhanced Rapid Syndromic Molecular Diagnostic Solution Detects Broad Range of Infectious Diseases
GenMark Diagnostics (Carlsbad, CA, USA), a member of the Roche Group (Basel, Switzerland), has rebranded its ePlex® system as the cobas eplex system. This rebranding under the globally renowned cobas name... Read more
Clinical Decision Support Software a Game-Changer in Antimicrobial Resistance Battle
Antimicrobial resistance (AMR) is a serious global public health concern that claims millions of lives every year. It primarily results from the inappropriate and excessive use of antibiotics, which reduces... Read morePathology
view channel
New AI Tool Classifies Brain Tumors More Quickly and Accurately
Precision in diagnosing and categorizing tumors is essential for delivering effective treatment to patients. Currently, the gold standard for identifying various types of brain tumors involves DNA methylation-based... Read more
AI Integrated With Optical Imaging Technology Enables Rapid Intraoperative Diagnosis
Rapid and accurate intraoperative diagnosis is essential for tumor surgery as it guides surgical decisions with precision. Traditional intraoperative assessments, such as frozen sections based on H&E... Read more
HPV Self-Collection Solution Improves Access to Cervical Cancer Testing
Annually, over 604,000 women across the world are diagnosed with cervical cancer, and about 342,000 die from this disease, which is preventable and primarily caused by the Human Papillomavirus (HPV).... Read more
Hyperspectral Dark-Field Microscopy Enables Rapid and Accurate Identification of Cancerous Tissues
Breast cancer remains a major cause of cancer-related mortality among women. Breast-conserving surgery (BCS), also known as lumpectomy, is the removal of the cancerous lump and a small margin of surrounding tissue.... Read moreTechnology
view channel
New Diagnostic System Achieves PCR Testing Accuracy
While PCR tests are the gold standard of accuracy for virology testing, they come with limitations such as complexity, the need for skilled lab operators, and longer result times. They also require complex... Read more
DNA Biosensor Enables Early Diagnosis of Cervical Cancer
Molybdenum disulfide (MoS2), recognized for its potential to form two-dimensional nanosheets like graphene, is a material that's increasingly catching the eye of the scientific community.... Read more
Self-Heating Microfluidic Devices Can Detect Diseases in Tiny Blood or Fluid Samples
Microfluidics, which are miniature devices that control the flow of liquids and facilitate chemical reactions, play a key role in disease detection from small samples of blood or other fluids.... Read more
Breakthrough in Diagnostic Technology Could Make On-The-Spot Testing Widely Accessible
Home testing gained significant importance during the COVID-19 pandemic, yet the availability of rapid tests is limited, and most of them can only drive one liquid across the strip, leading to continued... Read moreIndustry
view channel
Danaher and Johns Hopkins University Collaborate to Improve Neurological Diagnosis
Unlike severe traumatic brain injury (TBI), mild TBI often does not show clear correlations with abnormalities detected through head computed tomography (CT) scans. Consequently, there is a pressing need... Read more
Beckman Coulter and MeMed Expand Host Immune Response Diagnostics Partnership
Beckman Coulter Diagnostics (Brea, CA, USA) and MeMed BV (Haifa, Israel) have expanded their host immune response diagnostics partnership. Beckman Coulter is now an authorized distributor of the MeMed... Read more_1.jpg "Image: Thermo Fisher will distribute Bio-Techne products across Europe (Photo courtesy of 123RF)")
