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- Nordström, Lena, et al.
(författare)
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SOX11 and TP53 add prognostic information to MIPI in a homogenously treated cohort of mantle cell lymphoma : a Nordic Lymphoma Group study
- 2014
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 166:1, s. 98-108
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Tidskriftsartikel (refereegranskat)abstract
- Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma, where survival has been remarkably improved by use of protocols including high dose cytarabine, rituximab and autologous stem cell transplantation, such as the Nordic MCL2/3 protocols. In 2008, a MCL international prognostic index (MIPI) was created to enable stratification of the clinical diverse MCL patients into three risk groups. So far, use of the MIPI in clinical routine has been limited, as it has been shown that it inadequately separates low and intermediate risk group patients. To improve outcome and minimize treatment-related morbidity, additional parameters need to be evaluated to enable risk-adapted treatment selection. We have investigated the individual prognostic role of the MIPI and molecular markers including SOX11, TP53 (p53), MKI67 (Ki-67) and CCND1 (cyclin D1). Furthermore, we explored the possibility of creating an improved prognostic tool by combining the MIPI with information on molecular markers. SOX11 was shown to significantly add prognostic information to the MIPI, but in multivariate analysis TP53 was the only significant independent molecular marker. Based on these findings, we propose that TP53 and SOX11 should routinely be assessed and that a combined TP53/MIPI score may be used to guide treatment decisions.
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| 2. |
- Kuci, Venera, et al.
(författare)
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Emerging role of SOX11 in mantle cell lymphoma
- 2015
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Ingår i: Blood and Lymphatic Cancer: Targets and Therapy. - 1179-9889. ; 5, s. 35-41
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Forskningsöversikt (refereegranskat)abstract
- During recent years the neural transcription factor SOX11 has been established as an important biomarker for mantle cell lymphoma. SOX11 is both a diagnostic and prognostic antigen, and may potentially be used for treatment selection for younger patients, in relation to protocols including high dose chemotherapy. The molecular pathways involved are still not fully elucidated and, as SOX11 can interact with several co-transcription factors, functional assays need to be carefully designed to pinpoint SOX11-specific function in a defined cellular context. Furthermore, as SOX11 belongs to a large family of homologous proteins, analysis of SOX11 has been limited by the availability of specific antibodies for detection and pull-down. In this review, we discuss the emerging role of SOX11 in mantle cell lymphoma and discuss the potential impact in relation to tumorigenesis, diagnostics, prognostics, and therapy.
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| 3. |
- Nordström, Lena, et al.
(författare)
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Expanded clinical and experimental use of SOX11-using a monoclonal antibody
- 2012
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 12:269
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Tidskriftsartikel (refereegranskat)abstract
- Background: The transcription factor SOX11 is of diagnostic and prognostic importance in mantle cell lymphoma (MCL) and epithelial ovarian cancer (EOC), respectively. Thus, there is an unmet clinical and experimental need for SOX11-targeting assays with low background, high specificity and robust performance in multiple applications, including immunohistochemistry (IHC-P) and flow cytometry, which until now has been lacking. Methods: We have developed SOX11-C1, a monoclonal mouse antibody targeting SOX11, and successfully evaluated its performance in western blots (WB), IHC-P, fluorescence microscopy and flow cytometry. Results: We confirm the importance of SOX11 as a diagnostic antigen in MCL as 100% of tissue micro array (TMA) cases show bright nuclear staining, using the SOX11-C1 antibody in IHC-P. We also show that previous reports of weak SOX11 immunostaining in a fraction of hairy cell leukemias (HCL) are not confirmed using SOX11-C1, which is consistent with the lack of transcription. Thus, high sensitivity and improved specificity are demonstrated using the monoclonal SOX11-C1 antibody. Furthermore, we show for the first time that flow cytometry can be used to separate SOX11 positive and negative cell lines and primary tumors. Of note, SOX11-C1 shows no nonspecific binding to primary B or T cells in blood and thus, can be used for analysis of B and T cell lymphomas from complex clinical samples. Dilution experiments showed that low frequencies of malignant cells (similar to 1%) are detectable above background using SOX11 as a discriminant antigen in flow cytometry. Conclusions: The novel monoclonal SOX11-specific antibody offers high sensitivity and improved specificity in IHC-P based detection of MCL and its expanded use in flow cytometry analysis of blood and tissue samples may allow a convenient approach to early diagnosis and follow-up of MCL patients.
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