Top

Published in:

01-08-2017 | Original Article

SOX11 regulates the pro-apoptosis signal pathway and predicts a favorable prognosis of mantle cell lymphoma

Authors: Wenjuan Yang, Yanying Wang, Zhen Yu, Zengjun Li, Gang An, Wei Liu, Rui Lv, Liping Ma, Shuhua Yi, Lugui Qiu

Published in: International Journal of Hematology | Issue 2/2017

Abstract

Sex-determining region Y-box 11 (SOX11) is an important diagnostic marker in mantle cell lymphoma (MCL). However, the direct oncogenic mechanisms and downstream effector pathways implicated in SOX11-driven transformation remain poorly understood. In the present study, we analyzed SOX11 expression in B-NHL, and used lentivirus-mediated RNA interference targeting SOX11 to investigate the resulting changes in cellular processes and the underlying mechanisms in MCL cell lines. We found that patients with higher SOX11 expression have superior overall survival (OS) and progression-free survival (PFS) compared to those with lower SOX11 expression. SOX11 silencing promotes proliferation and inhibiting apoptosis of MCL cell through caspase-9-3-7-PARP signaling, and desensitizes MCL cell to bortezomib. Conclusively, our data suggest that SOX11 represents a useful prognostic marker in mantle cell lymphoma.

Campo E, Rule S. Mantle cell lymphoma: evolving management strategies. Blood. 2015;125:48–55.CrossRefPubMed

Barista I, Romaguera JE, Cabanillas F. Mantle-cell lymphoma. Lancet Oncol. 2001;2:141–8.CrossRefPubMed

Bodrug SE, Warner BJ, Bath ML, Lindeman GJ, Harris AW, Adams JM. Cyclin D1transgene impedes lymphocyte maturation and collaborates in lymphoma genesis with the myc gene. EMBO J. 1994;13:2124–30.PubMedPubMedCentral

Dy P, Penzo-Méndez A, Wang H, Pedraza CE, Macklin WB, Lefebvre V. The three SoxC proteins–Sox4, Sox11 and Sox12 exhibit overlapping expression patterns and molecular properties. Nucleic Acids Res. 2008;36:3101–17.CrossRefPubMedPubMedCentral

Bhattaram P, Penzo-Méndez A, Sock E, Colmenares C, Kaneko KJ, Vassilev A, et al. Organogenesis relies on SoxC transcription factors for the survival of neural and mesenchymal progenitors. Nat Commun. 2010;1:1–12.CrossRefPubMedCentral

Nordström L, Sernbo S, Eden P, Grønbaek K, Kolstad A, Räty R, et al. SOX11and TP53 add prognostic information to MIPI in a homogenously treated cohort of mantle cell lymphoma-a Nordic Lymphoma Group study. Br J Haematol. 2014;166:98–108.CrossRefPubMedPubMedCentral

Dictor M, Ek S, Sundberg M, Warenholt J, György C, Sernbo S, et al. Strong lymphoid nuclear expression of SOX11 transcription factor defines lymphoblastic neoplasms, mantle cell lymphoma and Burkitt’s lymphoma. Haematologica. 2009;94:1563–8.CrossRefPubMedPubMedCentral

Vegliante MC, Palomero J, Pérez-Galán P, Roué G, Castellano G, Navarro A, et al. SOX11 regulates PAX5 expression and blocks terminal B-cell differentiation in aggressive mantle cell lymphoma. Blood. 2013;121:2175–85.CrossRefPubMed

Palomero J, Vegliante MC, Eguileor A, Rodríguez ML, Balsas P, Martínez D, et al. SOX11 defines two different subtypes of mantle cell lymphoma through transcriptional regulation of BCL6. Leukemia. 2015;. doi:10.1038/leu.2015.355.PubMed

10.

Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: IARC Press; 2008.

11.

Yi S, Zou D, Li C, Zhong S, Chen W, Li Z, et al. High incidence of MYC and BCL2 abnormalities in mantle cell lymphoma, although only MYC abnormality predicts poor survival. Oncotarget. 2015;6(39):42362–71.PubMedPubMedCentral

12.

Binet JL, Auquier A, Dighiero G, Chastang C, Piguet H, Goasguen J, et al. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer. 1981;48:198–206.CrossRefPubMed

13.

Bergsland M, Werme M, Malewicz M, Perlmann T, Muhr J. The establishment of neuronal properties is controlled by Sox4 and Sox11. Genes Dev. 2006;20:3475–86.CrossRefPubMedPubMedCentral

14.

Weigle B, Ebner R, Temme A, Schwind S, Schmitz M, Kiessling A, et al. Highly specific overexpression of the transcription factor SOX11 in human malignant gliomas. Oncol Rep. 2005;13:139–44.PubMed

15.

Sernbo S, Gustavsson E, Brennan DJ, Gallagher WM, Rexhepaj E, Rydnert F, et al. The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation. BMC Cancer. 2011;11:405–14.CrossRefPubMedPubMedCentral

16.

Hide T, Takezaki T, Nakatani Y, Nakamura H, Kuratsu J, Kondo T. Sox11 prevents tumorigenesisof glioma-initiating cells by inducing neuronal differentiation. Cancer Res. 2009;69:7953–9.CrossRefPubMed

17.

Ek S, Dictor M, Jerkeman M, Jirström K, Borrebaeck CA. Nuclear expression of the non B-cell lineage Sox11 transcription factor identifies mantle cell lymphoma. Blood. 2008;111:800–5.CrossRefPubMed

18.

Simonsen AT, Schou M, Sørensen CD, Bentzen HH, Nyvold CG. SOX11, CCND1, BCL1/IgH and IgH-VDJ: a battle of minimal residual disease markers in mantle cell lymphoma? Leuk Lymphoma. 2015;56:2724–7.CrossRefPubMed

19.

Meggendorfer M, Kern W, Haferlach C, Haferlach T, Schnittger S. SOX11 overexpression is a specific marker for mantle cell lymphoma and correlates with t(11;14) translocation, CCND1 expression and an adverse prognosis. Leukemia. 2013;27:2388–91.CrossRefPubMed

20.

Teo AE, Chen Z, Miranda RN, McDonnell T, Medeiros LJ, McCarty N. Differential PAX5 levels promote malignant B-cell infiltration, progression and drug resistance, and predict a poorprognosis in MCL patients independent of CCND1. Leukemia. 2015;. doi:10.1038/leu.2015.140.PubMedPubMedCentral

21.

Zorn AM, Barish GD, Williams BO, Lavender P, Klymkowsky MW, Varmus HE. Regulation of Wnt signaling by Sox proteins: XSox17 alpha/beta and XSox3 physically interact with beta-catenin. Mol Cell. 1999;4:487–98.CrossRefPubMed

22.

Kuo PY, Leshchenko VV, Fazzari MJ, Perumal D, Gellen T, He T, et al. High-resolution chromatin immunoprecipitation(ChIP) sequencing reveals novel binding targets and prognostic role for SOX11 in mantle cell lymphoma. Oncogene. 2015;34:1231–40.CrossRefPubMed

23.

Pérez-Galán P, Mora-Jensen H, Weniger MA, Shaffer AL 3rd, Rizzatti EG, Chapman CM, et al. Bortezomib resistance in mantle cell lymphoma is associated with plasmacytic differentiation. Blood. 2011;117:542–52.CrossRefPubMedPubMedCentral

Title: SOX11 regulates the pro-apoptosis signal pathway and predicts a favorable prognosis of mantle cell lymphoma
Authors: Wenjuan Yang
Yanying Wang
Zhen Yu
Zengjun Li
Gang An
Wei Liu
Rui Lv
Liping Ma
Shuhua Yi
Lugui Qiu
Publication date: 01-08-2017
Publisher: Springer Japan
Published in: International Journal of Hematology / Issue 2/2017
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-017-2236-y

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2017

Germline ETV6 mutations and predisposition to hematological malignancies

Myeloid neoplasms with germline DDX41 mutation

JSH Guideline for Tumors of Hematopoietic and Lymphoid Tissues: Leukemia: 6. Myelodysplastic syndromes (MDS)

Heterogeneity of GATA2-related myeloid neoplasms

Myeloid neoplasms with germ line RUNX1 mutation

Successful treatment of histiocytic sarcoma with cladribine and high-dose cytosine arabinoside in a child

Keynote webinar | Spotlight on antibody–drug conjugates in cancer