TitleIdentification of LMO2 transcriptome and interactome in diffuse large B-cell lymphoma.
Publication TypeJournal Article
Year of Publication2012
AuthorsCubedo, Elena, Gentles Andrew J., Huang ChuanXin, Natkunam Yasodha, Bhatt Shruti, Lu Xiaoqing, Jiang Xiaoyu, Romero-Camarero Isabel, Freud Aharon, Zhao Shuchun, Bacchi Carlos E., Martinez-Climent Jose A., Sanchez-Garcia Isidro, Melnick Ari, and Lossos Izidore S.
Date Published2012 Jun 07
KeywordsAdaptor Proteins, Signal Transducing, B-Lymphocytes, Base Sequence, Cell Line, Cell Line, Tumor, Cell Proliferation, Centrosome, Gene Expression Regulation, Neoplastic, Humans, LIM Domain Proteins, Lymphoma, Large B-Cell, Diffuse, Molecular Sequence Data, Promoter Regions, Genetic, Proto-Oncogene Proteins, RNA, Long Noncoding, Transcriptome, Transferases, Tumor Suppressor Proteins

<p>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.</p>

Alternate JournalBlood
PubMed ID22517897
PubMed Central IDPMC3369683
Grant ListU56 CA112973 / CA / NCI NIH HHS / United States
CA122105 / CA / NCI NIH HHS / United States
R01 CA109335 / CA / NCI NIH HHS / United States
R01 CA122105 / CA / NCI NIH HHS / United States
CA109335 / CA / NCI NIH HHS / United States
R01 CA104348 / CA / NCI NIH HHS / United States