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Notch signaling is a potent inducer of growth arrest and apoptosis in a wide range of B-cell malignancies.

Publication ,  Journal Article
Zweidler-McKay, PA; He, Y; Xu, L; Rodriguez, CG; Karnell, FG; Carpenter, AC; Aster, JC; Allman, D; Pear, WS
Published in: Blood
December 1, 2005

Although Notch receptor expression on malignant B cells is widespread, the effect of Notch signaling in these cells is poorly understood. To investigate Notch signaling in B-cell malignancy, we assayed the effect of Notch activation in multiple murine and human B-cell tumors, representing both immature and mature subtypes. Expression of constitutively active, truncated forms of the 4 mammalian Notch receptors (ICN1-4) inhibited growth and induced apoptosis in both murine and human B-cell lines but not T-cell lines. Similar results were obtained in human precursor B-cell acute lymphoblastic leukemia lines when Notch activation was achieved by coculture with fibroblasts expressing the Notch ligands Jagged1 or Jagged2. All 4 truncated Notch receptors, as well as the Jagged ligands, induced Hes1 transcription. Retroviral expression of Hairy/Enhancer of Split-1 (Hes1) recapitulated the Notch effects, suggesting that Hes1 is an important mediator of Notch-induced growth arrest and apoptosis in B cells. Among the B-cell malignancies that were susceptible to Notch-mediated growth inhibition/apoptosis were mature B-cell and therapy-resistant B-cell malignancies, including Hodgkin, myeloma, and mixed-lineage leukemia (MLL)-translocated cell lines. These results suggest that therapies capable of activating Notch/Hes1 signaling may have therapeutic potential in a wide range of human B-cell malignancies.

Duke Scholars

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Published In

Blood

DOI

ISSN

0006-4971

Publication Date

December 1, 2005

Volume

106

Issue

12

Start / End Page

3898 / 3906

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Signal Transduction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptors, Notch
  • Mice
  • Lymphoproliferative Disorders
  • Immunology
  • Humans
  • Homeodomain Proteins
  • Cell Proliferation
 

Citation

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Zweidler-McKay, P. A., He, Y., Xu, L., Rodriguez, C. G., Karnell, F. G., Carpenter, A. C., … Pear, W. S. (2005). Notch signaling is a potent inducer of growth arrest and apoptosis in a wide range of B-cell malignancies. Blood, 106(12), 3898–3906. https://doi.org/10.1182/blood-2005-01-0355
Zweidler-McKay, Patrick A., Yiping He, Lanwei Xu, Carlos G. Rodriguez, Fredrick G. Karnell, Andrea C. Carpenter, Jon C. Aster, David Allman, and Warren S. Pear. “Notch signaling is a potent inducer of growth arrest and apoptosis in a wide range of B-cell malignancies.Blood 106, no. 12 (December 1, 2005): 3898–3906. https://doi.org/10.1182/blood-2005-01-0355.
Zweidler-McKay PA, He Y, Xu L, Rodriguez CG, Karnell FG, Carpenter AC, et al. Notch signaling is a potent inducer of growth arrest and apoptosis in a wide range of B-cell malignancies. Blood. 2005 Dec 1;106(12):3898–906.
Zweidler-McKay, Patrick A., et al. “Notch signaling is a potent inducer of growth arrest and apoptosis in a wide range of B-cell malignancies.Blood, vol. 106, no. 12, Dec. 2005, pp. 3898–906. Pubmed, doi:10.1182/blood-2005-01-0355.
Zweidler-McKay PA, He Y, Xu L, Rodriguez CG, Karnell FG, Carpenter AC, Aster JC, Allman D, Pear WS. Notch signaling is a potent inducer of growth arrest and apoptosis in a wide range of B-cell malignancies. Blood. 2005 Dec 1;106(12):3898–3906.

Published In

Blood

DOI

ISSN

0006-4971

Publication Date

December 1, 2005

Volume

106

Issue

12

Start / End Page

3898 / 3906

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Signal Transduction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptors, Notch
  • Mice
  • Lymphoproliferative Disorders
  • Immunology
  • Humans
  • Homeodomain Proteins
  • Cell Proliferation