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An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Impact of acquired del(17p) in multiple myeloma
Arjun Lakshman1, Utkarsh Painuly2, S Vincent Rajkumar1
1Division of Hematology, Mayo Clinic, Rochester, MN.
Abstract:
The high-risk abnormality del(17p) can be detected by fluorescence in situ hybridization on malignant plasma cells (PCs) and has an adverse prognostic impact in patients with multiple myeloma (MM). Patients with del(17p) have reduced overall survival (OS). Patients who acquire del(17p) later during the disease course are not well described. The disease characteristics at diagnosis predicting for acquired del(17p) and its overall impact on patient survival is not known. We compared 76 patients with MM who were negative for del(17p) at diagnosis and acquired it later with 152 control MM patients who did not acquire del(17p) at a comparable time point. Patients acquired del(17p) at a median of 35.6 months (range, 4.6-116.1 months) from diagnosis of MM after a median of 2 lines of therapy (range, 1-10 lines of therapy). When compared with controls, patients with acquired del(17p) had shorter median progression-free survival (PFS) (30.1 vs 23.0 months; P = .032) and OS (106.1 vs 68.2 months; P < .001) from diagnosis. After the detection of del(17p), the median PFS was 5.4 months and the median OS was 18.1 months. High lactate dehydrogenase level (odds ratio [OR], 3.69; 95% confidence interval [CI], 1.11-12.24) and presence of t(4;14) (OR, 2.66; 95% CI, 1.09-6.48) or any high-risk translocation (OR, 2.23; 95% CI, 1.00-4.95) at diagnosis predicted acquisition of del(17p). High PC proliferative rate predicted shorter OS from detection of del(17p) (hazard ratio, 2.28; 95% CI, 1.31-3.96; P = .004). Our study shows that acquisition of del(17p) is an important molecular event associated with reduction in OS in MM. Certain baseline factors may predict acquisition of del(17p). This needs validation in prospective data sets.
Insights
Acquiring the del(17p) genetic abnormality later in multiple myeloma (MM) significantly reduces overall survival (OS). High lactate dehydrogenase and certain translocations at diagnosis predict this acquisition, impacting MM patient outcomes.
Area of Science:
- Hematology
- Oncology
- Molecular Genetics
Background:
- The del(17p) genetic abnormality is a high-risk marker in multiple myeloma (MM), associated with reduced overall survival (OS).
- The prognostic impact and predictive factors for acquiring del(17p) later in the disease course are not well understood.
Purpose of the Study:
- To investigate the characteristics of patients who acquire del(17p) during MM progression.
- To determine the impact of acquired del(17p) on patient survival.
- To identify baseline disease characteristics that predict the acquisition of del(17p).
Main Methods:
- A comparative study involving 76 MM patients who acquired del(17p) and 152 controls who did not.
- Analysis of progression-free survival (PFS) and OS from diagnosis and from del(17p) detection.
- Statistical analysis to identify predictors of del(17p) acquisition and its impact on survival.
Main Results:
- Patients acquiring del(17p) had significantly shorter median PFS (23.0 vs 30.1 months) and OS (68.2 vs 106.1 months) from diagnosis compared to controls.
- After del(17p) detection, median PFS was 5.4 months and median OS was 18.1 months.
- High lactate dehydrogenase, t(4;14), or any high-risk translocation at diagnosis predicted del(17p) acquisition.
Conclusions:
- Acquisition of del(17p) is a critical molecular event in MM, significantly worsening patient prognosis and reducing OS.
- Specific baseline factors, including high LDH and certain translocations, can predict the later acquisition of del(17p).
- Further validation in prospective studies is needed to confirm these predictive factors and inform clinical management.
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