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
Nucleic Acid Extractor System
NEOS-96 XT
New
Pneumonia Test
Pneumocystis ELITe MGB® Kit
New
ACR Urine Test
On Call MultiPro ACR
Latest BioResearch News
- Disease Gene Discovery Advances Diagnosis of Rare Movement Disorders
- Genetic Discovery Could Improve Diagnosis of Drug-Resistant Epilepsy
- Genetic Discovery May Improve Diagnosis of Rare Dementia Subtype
- Mass Spectrometry Technique Detects Protein and Sugar Changes in Neurodegeneration
- Barcoded DNA Sheds Light on Hidden Complexities in Breast Cancer Detection
- CRISPR-Based Platform Pinpoints Drivers of Acute Myeloid Leukemia in Patient Cells
- Protective Brain Protein Emerges as Biomarker Target in Alzheimer’s Disease
- 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
Channels
Clinical Chemistry
view channel
New Plasma Tau Assay Improves Prediction of Alzheimer’s Progression
Predicting which patients with early symptomatic Alzheimer’s disease will decline more rapidly remains a key challenge in both research and patient care. Growing interest in tau biology, along with advances... Read more
Routine Blood Markers Predict Heart Failure Risk in Prediabetes
Heart failure prevention relies on finding high-risk adults before symptoms appear, yet effective stratification remains difficult in routine care. Prediabetes affects an estimated 115.2 million U.... Read more
Molecular Diagnostics
view channel
Liquid Biopsy Enables Faster Diagnosis of Childhood Cancer in Africa
Burkitt lymphoma is the most common childhood cancer in Africa and progresses rapidly, making fast, accurate diagnosis essential to survival. Although survival can exceed 90% when therapy starts quickly,... Read more
Blood Test Helps Guide Treatment in Older Women with Breast Cancer
Older women with estrogen receptor–positive breast cancer often face difficult decisions about treatment, especially when surgery and radiation can lead to side effects such as scarring, swelling, infection... Read more
Hematology
view channel
Rapid Cartridge-Based Test Aims to Expand Access to Hemoglobin Disorder Diagnosis
Sickle cell disease and beta thalassemia are hemoglobin disorders that often require referral to specialized laboratories for definitive diagnosis, delaying results for patients and clinicians.... Read more
New Guidelines Aim to Improve AL Amyloidosis Diagnosis
Light chain (AL) amyloidosis is a rare, life-threatening bone marrow disorder in which abnormal amyloid proteins accumulate in organs. Approximately 3,260 people in the United States are diagnosed... Read more
Immunology
view channel
Cancer Mutation ‘Fingerprints’ to Improve Prediction of Immunotherapy Response
Cancer cells accumulate thousands of genetic mutations, but not all mutations affect tumors in the same way. Some make cancer cells more visible to the immune system, while others allow tumors to evade... Read more
Immune Signature Identified in Treatment-Resistant Myasthenia Gravis
Myasthenia gravis is a rare autoimmune disorder in which immune attack at the neuromuscular junction causes fluctuating weakness that can impair vision, movement, speech, swallowing, and breathing.... Read more
New Biomarker Predicts Chemotherapy Response in Triple-Negative Breast Cancer
Triple-negative breast cancer is an aggressive form of breast cancer in which patients often show widely varying responses to chemotherapy. Predicting who will benefit from treatment remains challenging,... Read more
Blood Test Identifies Lung Cancer Patients Who Can Benefit from Immunotherapy Drug
Small cell lung cancer (SCLC) is an aggressive disease with limited treatment options, and even newly approved immunotherapies do not benefit all patients. While immunotherapy can extend survival for some,... Read moreMicrobiology
view channel
Breath Analysis Approach Offers Rapid Detection of Bacterial Infection
Accurate and rapid identification of bacterial infections remains challenging in acute care, where delays can hinder timely, targeted therapy. Infectious diseases are a major cause of mortality worldwide,... Read more
Study Highlights Accuracy Gaps in Consumer Gut Microbiome Kits
Direct-to-consumer gut microbiome kits promise personalized insights by profiling fecal bacteria and generating health readouts, but their analytical accuracy remains uncertain. A new study shows that... Read more
WHO Recommends Near POC Tests, Tongue Swabs and Sputum Pooling for TB Diagnosis
Tuberculosis (TB) remains one of the world’s leading infectious disease killers, yet millions of cases go undiagnosed or are detected too late. Barriers such as reliance on sputum samples, limited laboratory... Read more
Pathology
view channel
AI-Powered Tool to Transform Dermatopathology Workflow
Skin cancer accounts for the largest number of cancer diagnoses in the United States, placing sustained pressure on pathology services. Diagnostic interpretation can be variable for challenging melanocytic... Read more
New Chromogenic Culture Media Enable Rapid Detection of Candida Infections
Invasive Candida infections are challenging for healthcare systems, with some strains spreading rapidly in hospitals and showing resistance to multiple antifungal drugs. Candida auris is associated with... Read more
Technology
view channel
New Electronic Pipette Enhances Workflows with Touchscreen Control
Manual pipetting remains a routine yet error-prone step that can affect reproducibility and throughput in clinical and research laboratories. Training demands and ergonomic strain also add variability... Read more
AI Model Outperforms Clinicians in Rare Disease Detection
Rare diseases affect an estimated 300 million people worldwide, yet diagnosis is often protracted and error-prone. Many conditions present with heterogeneous signs that overlap with common disorders, leading... Read more
AI-Driven Diagnostic Demonstrates High Accuracy in Detecting Periprosthetic Joint Infection
Periprosthetic joint infection (PJI) is a rare but serious complication affecting 1% to 2% of primary joint replacement surgeries. The condition occurs when bacteria or fungi infect tissues around an implanted... Read more
Industry
view channel
Automated MSI Test Gains IVDR Certification to Guide CRC Therapy
Treatment selection for metastatic colorectal cancer often requires knowledge of a tumor’s microsatellite instability (MSI) status. Timely results can help clinicians decide on immunotherapy options.... Read more
