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
New
Gold Member
Pre- Eclampsia Control
Acusera Pre-Eclampsia Control
New
Platelet Function Analyzer
PL-12
Manual Pipetting Aid
Pipette Controllers macro
Latest BioResearch News
- D-Serine May Predict Immune Checkpoint Therapy Resistance in Gastric Cancer
- New Genetic Cause Identified for Neurodevelopmental Disorder
- New Genetic Discovery Could Support Precision Diabetes Care
- Inherited Genetic Differences Help Explain Variable CAR T-Cell Therapy Outcomes
- AI-Powered Genome Mapping Reveals New Layer of Alzheimer’s Disease Biology
- Genetic Variations Reveal Mechanisms Behind Sudden Cardiac Death Risk
- Immune Biomarkers Support Early Risk Stratification in Oral Precancer
- Global Genetic Map Identifies Regional Parkinson’s Variants to Support Diagnostics
- Breakthrough Genetic Map Advances Understanding of Bone Disorders
- Study Identifies Hereditary Subtype of Aggressive Prostate Cancer
- Gene Variants Linked to Pollution-Exacerbated Asthma
- Single-Cell Analysis Mapping Links Inflammation Response to Acute Myeloid Leukemia
- Study Reveals New Insights into Rare Blood Cancer Development
- New Findings Clarify Molecular Drivers of Rare Small Intestinal Cancer
- Lung Cancer Study Reveals Cellular Program Behind Therapy Resistance
Channels
Clinical Chemistry
view channel
Blood Test on a Chip Offers Low-Cost Lung Cancer Detection Without DNA Sequencing
Lung cancer is the leading cause of cancer deaths worldwide, and screening often yields indeterminate results that prompt invasive workups. Computed tomography (CT) detects small nodules but can flag benign... Read more
Portable Troponin Assay Brings Heart Attack Diagnosis Closer to Patients
Timely confirmation of myocardial infarction often depends on laboratory testing that may not be immediately available at the point of care. This gap between clinical suspicion and definitive evidence... Read more
Molecular Diagnostics
view channel
Whole-Cell Genomic Analysis Expands the Potential of Liquid Biopsy
Liquid biopsy has expanded access to tumor genomics, but most blood-based assays rely on short, degraded fragments of cell-free circulating tumor DNA (ctDNA). Isolating intact circulating tumor cells from... Read more
Blood Test Could Help Fast-Track Lymphoma Diagnosis in Resource-Limited Settings
Lymphoma can be difficult to distinguish from infections and benign conditions, while definitive diagnosis often depends on surgical tissue sampling and specialized pathology that may not be readily available.... Read more
Hematology
view channel
New Genetic Findings Reveal Cause of Bone Marrow Failure Syndrome
Inherited bone marrow failure syndromes (IBMFS) impair the bone marrow’s ability to produce sufficient healthy blood cells and are associated with an increased risk of early-onset myelodysplastic syndromes (MDS).... Read more
Ultra-Portable Device Enables Finger-Prick Blood Testing at Home
Patients who need frequent blood tests often face repeated clinic visits that burden services and disrupt care. In the UK, millions of tests are performed each year to diagnose disease, guide therapy,... Read more
Immunology
view channel
Study Reveals Viral Protein Driving COVID-19-Related Vascular Injury
Lingering symptoms after acute COVID-19 infection remain a clinical challenge, with many patients experiencing fatigue, cognitive problems, and cardiovascular complications months later.... Read more
Study Reveals Immune Mechanism Driving Severe COVID-19 Progression
Severe COVID-19 has highlighted gaps in understanding of early antiviral responses, particularly why some patients deteriorate despite timely care. Type I interferons are central to host defense, yet their... Read more
Antibody Profiling Identifies Preclinical Inflammatory Bowel Disease Years Before Diagnosis
Inflammatory bowel disease often develops after a prolonged symptom-free period, complicating timely recognition and clinical intervention. Limited understanding of immune activity during this silent phase... Read more
Microbiology
view channel
Precision Screening Helps Close Hepatitis C Diagnosis and Treatment Gaps
Hepatitis C remains a leading cause of cirrhosis and liver cancer, yet many infections go undiagnosed or untreated because health systems fail to reach those at greatest risk. Although highly effective... Read more
Proteomic Workflow Maps Microbial and Host Responses in Intestinal Inflammation
The intestinal microbiome influences digestion, metabolism, and immunity, yet its complexity makes functional measurements difficult to obtain. DNA surveys can indicate which organisms and potential pathways... Read more
Metagenomic Sequencing Enables Faster Diagnosis of Respiratory Infections in Cystic Fibrosis
Serious lung infections remain a major cause of morbidity among people with cystic fibrosis, a life-threatening genetic disorder characterized by persistent airway colonization and frequent antimicrobial exposure.... Read more
Pathology
view channel
FDA-Cleared Digital Pathology Platform Expands Interoperability for Primary Diagnosis
Rising cancer incidence is colliding with a shrinking pathologist workforce, intensifying pressure on diagnostic turnaround times in clinical laboratories. Many labs are adopting digital pathology to manage... Read more
AI Pathology Tool Predicts Relapse Risk in Stage II Colorectal Cancer
Bowel cancer is Australia’s fourth most commonly diagnosed cancer and the second leading cause of cancer death, while remaining the third most common cancer worldwide. In stage-two disease, determining... Read more
AI Pathology Tool Stratifies Rectal Cancer to Guide Chemoradiotherapy
Choosing intensified regimens for locally advanced rectal cancer is challenging because these therapies can cause serious side effects. Colorectal cancer is the fourth-most fatal cancer in the UK, and... Read more
PD-L1 Assay Guides Pembrolizumab Eligibility in Ovarian, Fallopian Tube, and Peritoneal Cancers
Agilent Technologies’ PD-L1 IHC 22C3 pharmDx (Code SK006) has received European Union certification as a companion diagnostic to aid in identifying patients with epithelial ovarian, fallopian tube, or... Read moreTechnology
view channel
Interoperable Data Platform Standardizes Multi-Cancer Blood Test Results
Proteotype Diagnostics has introduced Alchemi, a proprietary data and clinical workflow platform being developed for Enlighten, the company’s investigational blood-based multi-cancer test.... Read more
Training Device Improves Accuracy of Pooled Molecular Diagnostics
High-throughput molecular diagnostics have transformed infectious disease detection, but many workflows remain difficult to execute accurately without extensive training. Sample pooling can cut per‑test... Read more
New CE-Certified Software Advances Whole-Genome Cancer Testing
European hospitals are increasingly using comprehensive tumor genomics to guide therapy, but routine whole genome sequencing (WGS) requires validated, regulation-compliant workflows. A newly CE-certified... Read more
National Rare Disease Registry Standardizes Genetic and Clinical Data for Coordinated Care
Rare diseases collectively impose a significant clinical burden despite their individual rarity, often involving multisystem presentations and prolonged diagnostic journeys. Limited specialist expertise... Read moreIndustry
view channel
Standardized Staining Technology Advances Digital Pathology Workflows
Digital pathology is increasingly used to streamline cancer diagnostics, yet staining variability can hinder slide interpretation and limit the reliability of artificial intelligence tools.... Read more
Global Testing Service Advances Leukemia MRD Monitoring
KMT2A rearrangements drive aggressive subsets of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) and are associated with relapse and poor outcomes. As menin inhibitors enter clinical... Read more
