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| Status |
Public on Mar 13, 2019 |
| Title |
Multiple myeloma immunoglobulin lambda translocations portend poor prognosis |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
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. To better understand and identify these ‘high-risk’ cases, we analyzed the translocation landscape of myeloma from 795 newly-diagnosed patients by whole genome sequencing from the CoMMpass study. Translocations involving the immunoglobulin lambda (IgL) locus were identified in 10% of patients, and were indicative of poor prognosis. Importantly, 70% of IgL translocations co-occurred with hyperdiploid disease, a marker of standard risk, potentially resulting in the misclassification of IgL-translocated myeloma. Most IgL-translocations coincided with focal amplifications that were centered on the 3’ enhancer. Patients with IgL-translocations failed to benefit from immunomodulatory imide drugs (IMiDs), which target the lymphocyte-specific transcription factor IKZF1 that is bound to the IgL 3’ enhancer at some of the highest levels in the myeloma epigenome. These data implicate IgL-translocation as a driver of poor prognosis which may be due in part to IMID resistance.
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| Overall design |
Several myeloma cell lines were characterized for chromatin accessibility
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| Contributor(s) |
Barwick BG |
| Citation(s) |
31015454, 33649772 |
| Submission date |
Oct 29, 2018 |
| Last update date |
Mar 12, 2021 |
| Contact name |
Benjamin G Barwick |
| E-mail(s) |
benjamin.barwick@emory.edu
|
| Phone |
(404) 285-2964
|
| Organization name |
Emory University
|
| Department |
Hematology and Medical Oncology
|
| Lab |
Barwick Lab
|
| Street address |
1365 Clifton Rd. NE WCI-C 4th Floor Benches 36-37
|
| City |
Atlanta |
| State/province |
GA |
| ZIP/Postal code |
30322 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (28)
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| Relations |
| BioProject |
PRJNA499054 |
| SRA |
SRP167124 |
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