Identification of LMO2 transcriptome and interactome in diffuse large B-cell,lymphoma

Elena Cubedo, Andrew J. Gentles, Chuanxin Huang, Yasodha Natkunam, Shruti Bhatt, Xiaoqing Lu, Xiaoyu Jiang, Isabel Romero-Camarero, Aharon Freud, Shuchun Zhao, Carlos E. Bacchi, Jose A. Martínez-Climent, Isidro Sanchez-García, Ari Melnick, Izidore S. Lossos

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

LMO2 regulates gene expression by facilitating the formation of multipartite DNA-binding complexes. In B cells, LMO2 is specifically up-regulated in the germinal center (GC) and is expressed in GC-derived non-Hodgkin lymphomas. LMO2 is one of the most powerful prognostic indicators in diffuse large B-cell (DLBCL) patients. However, its function in GC B cells and DLBCL is currently unknown. In this study, we characterized the LMO2 transcriptome and transcriptional complex in DLBCL cells. LMO2 regulates genes implicated in kinetochore function, chromosome assembly, and mitosis. Overexpression of LMO2 in DLBCL cell lines results in centrosome amplification. In DLBCL, the LMO2 complex contains some of the traditional partners, such as LDB1, E2A, HEB, Lyl1, ETO2, and SP1, but not TAL1 or GATA proteins. Furthermore, we identified novel LMO2 interacting partners: ELK1, nuclear factor of activated T-cells (NFATc1), and lymphoid enhancer-binding factor1 (LEF1) proteins. Reporter assays revealed that LMO2 increases transcriptional activity of NFATc1 and decreases transcriptional activity of LEF1 proteins. Overall, our studies identified a novel LMO2 transcriptome and interactome in DLBCL and provides a platform for future elucidation of LMO2 function in GC B cells and DLBCL pathogenesis.

Original languageEnglish (US)
Pages (from-to)5478-5491
Number of pages14
JournalBlood
Volume119
Issue number23
DOIs
StatePublished - Jun 7 2012

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Cubedo, E., Gentles, A. J., Huang, C., Natkunam, Y., Bhatt, S., Lu, X., Jiang, X., Romero-Camarero, I., Freud, A., Zhao, S., Bacchi, C. E., Martínez-Climent, J. A., Sanchez-García, I., Melnick, A., & Lossos, I. S. (2012). Identification of LMO2 transcriptome and interactome in diffuse large B-cell,lymphoma. Blood, 119(23), 5478-5491. https://doi.org/10.1182/blood-2012-01-403154