The major vault protein (MVP), a new multidrug resistance associated protein, is frequently expressed in multiple myeloma
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L M Rimsza1, K Campbell, W S Dalton
1Department of Pathology, University of Florida, Gainesville, USA.
Abstract:
The major vault protein (MVP), a ribonucleoprotein complex which mediates the transport of xenobiotic toxins, has been implicated in multidrug resistance (MDR) not mediated by p-glycoprotein (P-gp) or multidrug resistance related protein (MRP). We evaluated, via immunohistochemistry, the presence of MVP in plasma cells of myeloma patients. Among 73 patients registered with the Southwest Oncology Group (SWOG), 52 patients (74%) were positive for MVP. The presence of MVP and P-gp were significantly associated (p < 0.01). A univariate analysis of response versus MVP positivity showed borderline statistical significance (p = 0.043) with no association with OS or PFS. In particular, MVP positivity at first biopsy was associated with non-responsiveness to therapy (7/7 patients, 100%). MRP was not present in any of 23 samples tested. An increased proliferative rate (Ki-67 > 5%) was significantly associated with shorter OS (log rank p-value = 0.0002). The collective work indicates that MVP protein is common and abundant in myeloma with potential relevance to therapeutic response.
Insights
Major vault protein (MVP) is common in myeloma, potentially impacting treatment resistance. MVP positivity in myeloma patients was linked to non-responsiveness to therapy, suggesting its role in therapeutic outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The major vault protein (MVP) is a ribonucleoprotein complex involved in xenobiotic toxin transport.
- MVP has been implicated in multidrug resistance (MDR) independent of P-glycoprotein (P-gp) or multidrug resistance related protein (MRP).
Purpose of the Study:
- To evaluate the presence and significance of MVP in plasma cells of myeloma patients.
- To investigate the association between MVP expression and therapeutic response, overall survival (OS), and progression-free survival (PFS).
Main Methods:
- Immunohistochemistry was used to detect MVP expression in plasma cells from 73 myeloma patients.
- Statistical analyses, including univariate analysis and log-rank tests, were performed to assess associations.
Main Results:
- MVP was detected in 74% (52/73) of myeloma patients.
- MVP positivity was significantly associated with P-gp expression (p < 0.01).
- MVP positivity showed borderline significance with treatment response (p = 0.043) and was associated with non-responsiveness at first biopsy (100%).
- Increased Ki-67 proliferation index was linked to shorter OS (p = 0.0002).
- MRP was not detected in tested samples.
Conclusions:
- MVP is common and abundant in myeloma.
- MVP expression may be relevant to therapeutic response and resistance in myeloma patients.
- Further investigation into MVP's role in myeloma pathogenesis and treatment is warranted.
