Sox11 augments bcr signaling to drive mcl-like tumor development

Pei Yu Kuo, Shashidhar S. Jatiani, Adeeb H. Rahman, Donna Edwards, Zewei Jiang, Katya Ahr, Deepak Perumal, Violetta V. Leshchenko, Joshua Brody, Rita Shaknovich, B. Hilda Ye, Samir Parekh

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Mantle cell lymphoma (MCL) is characterized by increased B-cell receptor (BCR) signaling, and BTK inhibition is an effective therapeutic intervention in MCL patients. The mechanisms leading to increased BCR signaling in MCL are poorly understood, as mutations in upstream regulators of BCR signaling such as CD79A, commonly observed in other lymphomas, are rare in MCL. The transcription factor SOX11 is overexpressed in the majority (78% to 93%) of MCL patients and is considered an MCL-specific oncogene. So far, attempts to understand SOX11 function in vivo have been hampered by the lack of appropriate animal models, because germline deletion of SOX11 is embryonically lethal. We have developed a transgenic mouse model (Em-SOX11-EGFP) in the C57BL/6 background expressing murine SOX11 and EGFP under the control of a B-cell–specific IgH-Em enhancer. The overexpression of SOX11 exclusively in B cells exhibits oligoclonal B-cell hyperplasia in the spleen, bone marrow, and peripheral blood, with an immunophenotype (CD51CD191CD232) identical to human MCL. Furthermore, phosphocytometric time-of-flight analysis of the splenocytes from these mice shows hyperactivation of pBTK and other molecules in the BCR signaling pathway, and serial bone marrow transplant from transgenic donors produces lethality with decreasing latency. We report here that overexpression of SOX11 in B cells promotes BCR signaling and a disease phenotype that mimics human MCL.

Original languageEnglish (US)
Pages (from-to)2247-2255
Number of pages9
JournalBlood
Volume131
Issue number20
DOIs
StatePublished - May 17 2018

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'Sox11 augments bcr signaling to drive mcl-like tumor development'. Together they form a unique fingerprint.

  • Cite this

    Kuo, P. Y., Jatiani, S. S., Rahman, A. H., Edwards, D., Jiang, Z., Ahr, K., Perumal, D., Leshchenko, V. V., Brody, J., Shaknovich, R., Ye, B. H., & Parekh, S. (2018). Sox11 augments bcr signaling to drive mcl-like tumor development. Blood, 131(20), 2247-2255. https://doi.org/10.1182/blood-2018-02-832535