Notch1 co-opts lymphoid enhancer factor 1 for survival of murine T-cell lymphomas

Christina Spaulding, Erica J. Reschly, Derek E. Zagort, Yumi Yashiro-Ohtani, Levi J. Beverly, Anthony J Capobianco, Warren S. Pear, Barbara L. Kee

Research output: Contribution to journalArticle

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Abstract

Oncogenic Notch1 mutations are found in most T-lineage acute lymphoblastic leukemias in humans and T-cell lymphomas in mice. However, the mechanism by which Notch1 promotes transformation or maintains malignant cell survival has not been determined fully. Here, we report that expression of the transcription factor lymphoid enhancer factor 1 (Lef1) is Notch dependent in murine T-cell lymphomas in vitro and in vivo, and that the intracellular domain of Notch1 (ICN1) is present at the Lef1 promoter. Lef1 expression is not Notch dependent in primary T-cell progenitors, but Lef1 mRNA is increased by ectopic expression of ICN1 in these cells. We show that Lef1 is required for survival of T-cell lymphoma lines, and that ectopic expression of Lef1 delays lymphoma cell death in the absence of Notch signaling, indicating that Lef1 is an important Notch target in these cells. Therefore, Notch1 co-opts Lef1 during the process of transformation to maintain survival of T-cell lymphomas.

Original languageEnglish
Pages (from-to)2650-2658
Number of pages9
JournalBlood
Volume110
Issue number7
DOIs
StatePublished - Oct 1 2007
Externally publishedYes

Fingerprint

TCF Transcription Factors
T-cells
T-Cell Lymphoma
Survival
Cell death
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma
Cell Survival
Cell Death
Transcription Factors
Cells
T-Lymphocytes
Cell Line
Messenger RNA
Mutation

ASJC Scopus subject areas

  • Hematology

Cite this

Spaulding, C., Reschly, E. J., Zagort, D. E., Yashiro-Ohtani, Y., Beverly, L. J., Capobianco, A. J., ... Kee, B. L. (2007). Notch1 co-opts lymphoid enhancer factor 1 for survival of murine T-cell lymphomas. Blood, 110(7), 2650-2658. https://doi.org/10.1182/blood-2007-04-084202

Notch1 co-opts lymphoid enhancer factor 1 for survival of murine T-cell lymphomas. / Spaulding, Christina; Reschly, Erica J.; Zagort, Derek E.; Yashiro-Ohtani, Yumi; Beverly, Levi J.; Capobianco, Anthony J; Pear, Warren S.; Kee, Barbara L.

In: Blood, Vol. 110, No. 7, 01.10.2007, p. 2650-2658.

Research output: Contribution to journalArticle

Spaulding, C, Reschly, EJ, Zagort, DE, Yashiro-Ohtani, Y, Beverly, LJ, Capobianco, AJ, Pear, WS & Kee, BL 2007, 'Notch1 co-opts lymphoid enhancer factor 1 for survival of murine T-cell lymphomas', Blood, vol. 110, no. 7, pp. 2650-2658. https://doi.org/10.1182/blood-2007-04-084202
Spaulding C, Reschly EJ, Zagort DE, Yashiro-Ohtani Y, Beverly LJ, Capobianco AJ et al. Notch1 co-opts lymphoid enhancer factor 1 for survival of murine T-cell lymphomas. Blood. 2007 Oct 1;110(7):2650-2658. https://doi.org/10.1182/blood-2007-04-084202
Spaulding, Christina ; Reschly, Erica J. ; Zagort, Derek E. ; Yashiro-Ohtani, Yumi ; Beverly, Levi J. ; Capobianco, Anthony J ; Pear, Warren S. ; Kee, Barbara L. / Notch1 co-opts lymphoid enhancer factor 1 for survival of murine T-cell lymphomas. In: Blood. 2007 ; Vol. 110, No. 7. pp. 2650-2658.
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AB - Oncogenic Notch1 mutations are found in most T-lineage acute lymphoblastic leukemias in humans and T-cell lymphomas in mice. However, the mechanism by which Notch1 promotes transformation or maintains malignant cell survival has not been determined fully. Here, we report that expression of the transcription factor lymphoid enhancer factor 1 (Lef1) is Notch dependent in murine T-cell lymphomas in vitro and in vivo, and that the intracellular domain of Notch1 (ICN1) is present at the Lef1 promoter. Lef1 expression is not Notch dependent in primary T-cell progenitors, but Lef1 mRNA is increased by ectopic expression of ICN1 in these cells. We show that Lef1 is required for survival of T-cell lymphoma lines, and that ectopic expression of Lef1 delays lymphoma cell death in the absence of Notch signaling, indicating that Lef1 is an important Notch target in these cells. Therefore, Notch1 co-opts Lef1 during the process of transformation to maintain survival of T-cell lymphomas.

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