Gene Translocation Marker Linked to Drug Resistance and Poor Prognosis
|
By LabMedica International staff writers Posted on 29 Apr 2019 |
|
Image: A histopathological image of multiple myeloma from a bone marrow aspirate (Photo courtesy of Wikimedia Commons).
Cancer researchers have identified a genetic marker linked to the likelihood of a bad prognosis for some patients suffering from multiple myeloma.
Multiple myeloma is a malignancy of antibody-secreting plasma cells. Most patients benefit from current therapies, however, 20% of patients relapse or die within two years and are deemed high risk.
To better understand the mechanisms that promote development of resistance to immunomodulatory drugs such as lenalidomide, investigators at Emory University School of Medicine (Atlanta, GA, USA) analyzed structural variants from 795 newly-diagnosed myeloma patients participating in the CoMMPass (Clinical Outcomes in Multiple Myeloma to Personal Assessment) study.
Results revealed that translocations involving the immunoglobulin lambda (IgL) gene locus were present in 10% of patients, and indicative of poor prognosis. This was particularly true for IgL-MYC gene translocations, which coincided with focal amplifications of enhancers at both loci. Importantly, 78% of IgL-MYC translocations co-occurred with hyperdiploid disease, a marker of standard risk, suggesting that IgL-MYC-translocated myelomas were being misclassified.
In addition, patients with myelomas carrying IgL translocations derived no survival benefit from immunomodulatory drugs such as lenalidomide. This may be because the IgL gene's activity was resistant to the mechanism of action of those drugs, or because the lenalidomide family of drugs promotes the destruction of Ikaros proteins, which bind especially tightly to the IgL gene locus.
"This [IgL translocation] could be different than other markers that we currently use in myeloma, because it may influence which drugs physicians may choose in both initial treatment as well as maintenance therapy," said senior author Dr. Lawrence Boise, professor of hematology and medical oncology at Emory University School of Medicine. "Most patients who have an IgL translocation are actually being diagnosed as having standard risk disease, so this study has helped explain why some patients who we think will do well end up relapsing and dying early."
The study was published in the April 23, 2019, online edition of the journal Nature Communications.
Related Links:
Emory University School of Medicine
Multiple myeloma is a malignancy of antibody-secreting plasma cells. Most patients benefit from current therapies, however, 20% of patients relapse or die within two years and are deemed high risk.
To better understand the mechanisms that promote development of resistance to immunomodulatory drugs such as lenalidomide, investigators at Emory University School of Medicine (Atlanta, GA, USA) analyzed structural variants from 795 newly-diagnosed myeloma patients participating in the CoMMPass (Clinical Outcomes in Multiple Myeloma to Personal Assessment) study.
Results revealed that translocations involving the immunoglobulin lambda (IgL) gene locus were present in 10% of patients, and indicative of poor prognosis. This was particularly true for IgL-MYC gene translocations, which coincided with focal amplifications of enhancers at both loci. Importantly, 78% of IgL-MYC translocations co-occurred with hyperdiploid disease, a marker of standard risk, suggesting that IgL-MYC-translocated myelomas were being misclassified.
In addition, patients with myelomas carrying IgL translocations derived no survival benefit from immunomodulatory drugs such as lenalidomide. This may be because the IgL gene's activity was resistant to the mechanism of action of those drugs, or because the lenalidomide family of drugs promotes the destruction of Ikaros proteins, which bind especially tightly to the IgL gene locus.
"This [IgL translocation] could be different than other markers that we currently use in myeloma, because it may influence which drugs physicians may choose in both initial treatment as well as maintenance therapy," said senior author Dr. Lawrence Boise, professor of hematology and medical oncology at Emory University School of Medicine. "Most patients who have an IgL translocation are actually being diagnosed as having standard risk disease, so this study has helped explain why some patients who we think will do well end up relapsing and dying early."
The study was published in the April 23, 2019, online edition of the journal Nature Communications.
Related Links:
Emory University School of Medicine
Gold Member
Nucleic Acid Extractor System
NEOS-96 XT
New
Clinical Informatics Platform
CLARION™
New
All-in-One Molecular System
AIO M160
Latest BioResearch News
- Common White Blood Cells Produce Schizophrenia-Linked Protein
- Nanopore Method Captures RNA Folding at Single-Molecule Resolution
- Tumor Microenvironment Marker Linked to Worse Survival in Solid Tumors
- Hidden Immune Gene Defect May Explain Kaposi Sarcoma Susceptibility
- Genetic Markers May Help Predict Amputation Risk in Peripheral Artery Disease
- Gene Signature Shows Promise for Depression Biomarker Testing
- AI-Driven Tumor Profiling Initiative Targets Precision Therapy Development
- Researchers Map Protein and Glycosylation Across 15 Human Body Fluids
- Telomere Length Abnormalities Linked to Lymphoma Development
- Biomarker Signals Chemotherapy Resistance in Relapsed Small Cell Lung Cancer
- Inflammatory Gene Signature Links Metabolic Disease to Pancreatic Cancer Recurrence
- Study Links Abnormal Gene Splicing to Treatment Response in Metastatic Kidney Cancer
- Research Reveals How Some Aplastic Anemia Patients Recover Bone Marrow Function
- New Molecular Insights Support Diagnosis of Hodgkin Lymphoma
- Epigenetic Signals and Blood Markers Aid Chronic Fatigue Syndrome Diagnosis
- Microenvironment Biomarkers Could Enable Early Lung Cancer Detection
Channels
Clinical Chemistry
view channel
International Experts Recommend Ending Routine 'Corrected' Calcium Reporting
Interpreting serum calcium can be clinically challenging when albumin levels vary, especially in patients with chronic illness or kidney disease. For decades, laboratories have used formulas to adjust... Read more
Long-Term Data Show PSA Screening Modestly Reduces Prostate Cancer Deaths
Prostate cancer is among the most common cancers in men, and the role of population screening has remained controversial because of overdiagnosis and overtreatment. Health systems have sought clearer,... Read more
Molecular Diagnostics
view channel
Expanded DPYD Genotyping Test Supports Safer Chemotherapy Dosing
Fluoropyrimidines such as 5-fluorouracil (5-FU) are chemotherapy drugs prescribed to more than two million cancer patients each year, but 10–20% of patients can experience severe, and sometimes fatal,... Read more
Multi-Omics Profiling Helps Predict BCG Response and Recurrence in Bladder Cancer
High-risk non–muscle-invasive bladder cancer frequently recurs after therapy, with about 30% of patients relapsing and roughly 10% dying within two years despite tumor resection, surveillance, and Bacillus... Read more
Hematology
view channel
Stem Cell Biomarkers May Guide Precision Treatment in Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is an aggressive blood cancer that most often affects older adults and still carries a poor prognosis despite therapeutic advances. Venetoclax-based regimens have improved... Read more
Advanced CBC-Derived Indices Integrated into Hematology Platforms
Diatron, a STRATEC brand, has introduced six advanced hematological indices on its Aquila, Aquarius 3, and Abacus 5 hematology analyzers. The new Research Use Only (RUO) indices include Neutrophil-to-Lymphocyte... Read more
Immunology
view channel
Simple Blood Test Could Replace Biopsies for Lung Transplant Rejection Monitoring
Lung transplant recipients face some of the highest rates of acute cellular rejection, and routine surveillance often relies on repeated surgical biopsies. These procedures can cause complications such... Read more
Routine TB Screening Test May Reveal Immune Aging and Mortality Risk
Immune aging is associated with weaker responses to vaccination, greater risks of infection, and higher levels of inflammation. Leveraging routinely ordered laboratory tests to quantify that responsiveness... Read more
Microbiology
view channel
Study Finds Hidden Mpox Infections May Drive Ongoing Spread
Mpox continues to circulate despite vaccination, and many cases show no known link to a symptomatic partner. The role of people without symptoms has remained uncertain, limiting clarity on how transmission persists.... Read more
Large-Scale Genomic Surveillance Tracks Resistant Bacteria Across European Hospitals
Antimicrobial resistance (AMR) poses a growing threat to patient safety, with carbapenem-resistant Enterobacterales causing difficult-to-treat infections and leaving clinicians with limited therapeutic options.... Read more
Molecular Urine and Stool Tests Do Not Improve Early TB Treatment in Hospitalized HIV Patients
Tuberculosis is the leading cause of death among people living with HIV, and diagnosis in hospital settings remains difficult. Symptoms are often non-specific, disease can be extrapulmonary, and many patients... Read more
Pathology
view channel
Rapid AI Tool Predicts Cancer Spatial Gene Expression from Pathology Images
Gene expression profiling can inform tumor biology and treatment selection, but spatial assays remain costly and time-consuming. Results can take weeks and cost thousands of dollars, limiting large-scale... Read more
AI Pathology Test Receives FDA Breakthrough for Bladder Cancer Risk Stratification
Non–muscle invasive bladder cancer has highly variable outcomes, complicating surveillance and treatment planning. Risk assessment typically relies on stage, grade, and tumor size, leaving uncertainty... Read more
Technology
view channel
AI Tool Automates Validation of Laboratory Software Configuration Changes
Regulated laboratories face heavy documentation and requalification demands when software configurations change, slowing improvements and discouraging beneficial updates. A new capability now automates... Read more
Point-of-Care Testing Enhances Health Literacy and Self-Management in Chronic Disease
Limited access to general practitioners and pathology services can delay diagnosis and monitoring for people in regional and remote communities. Rapid, on-the-spot testing can shorten turnaround times... Read more
Industry
view channel
Partnership Brings Single-Cell Analysis into Clinical Oncology Workflows
Selecting treatments for advanced cancer remains difficult when bulk analyses mask the functional diversity of tumor cells and mechanisms of resistance that emerge over time. Clinicians increasingly need... Read more
