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Lymphomas

Gene expression profiling of precursor T-cell lymphoblastic leukemia/lymphoma identifies oncogenic pathways that are potential therapeutic targets

Leukemia volume 21, pages 1276–1284 (2007)Cite this article

Abstract

We compared the gene expression pattern of thymic tumors from precursor T-cell lymphoblastic lymphoma/leukemia (pre-T LBL) that arose in transgenic mice that overexpressed SCL, LMO1 or NUP98-HOXD13 (NHD13) with that of thymocytes from normal littermates. Only two genes, Ccl8 and Mrpl38, were consistently more than fourfold overexpressed in pre-T LBL from all three genotypes analyzed, and a single gene, Prss16 was consistently underexpressed. However, we identified a number of genes, such as Cfl1, Tcra, Tcrb, Pbx3, Eif4a, Eif4b and Cox8b that were over or under-expressed in pre-T LBL that arose in specific transgenic lines. Similar to the situation seen with human pre-T LBL, the SCL/LMO1 leukemias displayed an expression profile consistent with mature, late cortical thymocytes, whereas the NHD13 leukemias displayed an expression profile more consistent with immature thymocytes. We evaluated two of the most differentially regulated genes as potential therapeutic targets. Cfl1 was specifically overexpressed in SCL-LMO1 tumors; inactivation of Cfl1 using okadaic acid resulted in suppression of leukemic cell growth. Overexpression of Ccl8 was a consistent finding in all three transgenic lines, and an antagonist for the Ccl8 receptor-induced death of leukemic cell lines, suggesting a novel therapeutic approach.

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Acknowledgements

We thank our colleague, Drs Li Li, Christopher Slape, Zhenhua Zhang and Helge Hartung for technical advices. We also greatly appreciate Dr Masue Hayashi's significant discussion. This research was supported by the Intramural Research Program of the NIH, NCI.

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Authors and Affiliations

  1. Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Navy8/Rm5105, 8901 Wisconsin Avenue, Bethesda, MD, USA

    Y-W Lin & P D Aplan

  2. Department of Pediatrics, Tenri Hospital, 200 Mishima-cho, Tenri, Nara, Japan

    Y-W Lin

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  1. Y-W Lin
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  2. P D Aplan
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Correspondence to P D Aplan.

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Lin, YW., Aplan, P. Gene expression profiling of precursor T-cell lymphoblastic leukemia/lymphoma identifies oncogenic pathways that are potential therapeutic targets. Leukemia 21, 1276–1284 (2007). https://doi.org/10.1038/sj.leu.2404685

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