A novel Notch ligand, Dll4, induces T-cell leukemia/lymphoma when overexpressed in mice by retroviral-mediated gene transfer - PubMed (original) (raw)

. 2001 Dec 15;98(13):3793-9.

doi: 10.1182/blood.v98.13.3793.

Affiliations

• PMID: 11739188
• DOI: 10.1182/blood.v98.13.3793

Free article

A novel Notch ligand, Dll4, induces T-cell leukemia/lymphoma when overexpressed in mice by retroviral-mediated gene transfer

X Q Yan et al. Blood. 2001.

Free article

Abstract

Notch receptors mediate cell-fate decisions through interaction with specific ligands during development. The biological role of a novel Notch ligand, Dll4, in mice was explored by reconstituting lethally irradiated mice with bone marrow (BM) cells transduced with Dll4 retroviral vector. White blood cell and lymphocyte counts in Dll4-overexpressing mice were reduced at the early stage of reconstitution but increased significantly at approximately 10 weeks after BM transplantation. BM, spleen, lymph nodes, and peripheral blood of Dll4-overexpressing mice contained predominantly CD4(+)CD8(+) T cells and virtually lacked B cells. The Dll4-overexpressing mice eventually developed a lethal phenotype that was characterized by the progression of a T-cell lymphoproliferative disease (restricted to BM and lymphoid tissues) to transplantable monoclonal T-cell leukemia/lymphoma scattered to multiple organs. Results suggest that the interaction of Dll4 with Notch1 may provide key signals for T-cell development.

PubMed Disclaimer

Similar articles

• Characterization of two distinct lymphoproliferative diseases caused by ectopic expression of the Notch ligand DLL4 on T cells.
  Xiong H, Maraver A, Latkowski JA, Henderson T, Schlessinger K, Ding Y, Shen J, Tadokoro CE, Lafaille JJ. Xiong H, et al. PLoS One. 2013 Dec 27;8(12):e84841. doi: 10.1371/journal.pone.0084841. eCollection 2013. PLoS One. 2013. PMID: 24386421 Free PMC article.
• DLL4 regulates NOTCH signaling and growth of T acute lymphoblastic leukemia cells in NOD/SCID mice.
  Minuzzo S, Agnusdei V, Pusceddu I, Pinazza M, Moserle L, Masiero M, Rossi E, Crescenzi M, Hoey T, Ponzoni M, Amadori A, Indraccolo S. Minuzzo S, et al. Carcinogenesis. 2015 Jan;36(1):115-21. doi: 10.1093/carcin/bgu223. Epub 2014 Oct 29. Carcinogenesis. 2015. PMID: 25355291
• Ectopic expression of Delta4 impairs hematopoietic development and leads to lymphoproliferative disease.
  Dorsch M, Zheng G, Yowe D, Rao P, Wang Y, Shen Q, Murphy C, Xiong X, Shi Q, Gutierrez-Ramos JC, Fraser C, Villeval JL. Dorsch M, et al. Blood. 2002 Sep 15;100(6):2046-55. Blood. 2002. PMID: 12200365
• Retroviral-mediated expression of an MHC class I-restricted T cell receptor in the CD8 T cell compartment of bone marrow-reconstituted mice.
  Pogulis RJ, Hansen MJ, Pease LR. Pogulis RJ, et al. Hum Gene Ther. 1998 Oct 10;9(15):2285-97. doi: 10.1089/hum.1998.9.15-2285. Hum Gene Ther. 1998. PMID: 9794212
• Potential use of T cell receptor genes to modify hematopoietic stem cells for the gene therapy of cancer.
  Clay TM, Custer MC, Spiess PJ, Nishimura MI. Clay TM, et al. Pathol Oncol Res. 1999;5(1):3-15. doi: 10.1053/paor.1999.0003. Pathol Oncol Res. 1999. PMID: 10079371 Review.

Cited by

• Normalization of the tumor microenvironment by harnessing vascular and immune modulation to achieve enhanced cancer therapy.
  Choi Y, Jung K. Choi Y, et al. Exp Mol Med. 2023 Nov;55(11):2308-2319. doi: 10.1038/s12276-023-01114-w. Epub 2023 Nov 1. Exp Mol Med. 2023. PMID: 37907742 Free PMC article. Review.
• A double-negative thymocyte-specific enhancer augments Notch1 signaling to direct early T cell progenitor expansion, lineage restriction and β-selection.
  Kashiwagi M, Figueroa DS, Ay F, Morgan BA, Georgopoulos K. Kashiwagi M, et al. Nat Immunol. 2022 Nov;23(11):1628-1643. doi: 10.1038/s41590-022-01322-y. Epub 2022 Oct 31. Nat Immunol. 2022. PMID: 36316479 Free PMC article.
• DLL1 orchestrates CD8+ T cells to induce long-term vascular normalization and tumor regression.
  Zhang N, Yin R, Zhou P, Liu X, Fan P, Qian L, Dong L, Zhang C, Zheng X, Deng S, Kuai J, Liu Z, Jiang W, Wang X, Wu D, Huang Y. Zhang N, et al. Proc Natl Acad Sci U S A. 2021 Jun 1;118(22):e2020057118. doi: 10.1073/pnas.2020057118. Proc Natl Acad Sci U S A. 2021. PMID: 34035167 Free PMC article.
• Spleen plays a major role in DLL4-driven acute T-cell lymphoblastic leukemia.
  Xiong H, Mancini M, Gobert M, Shen S, Furtado GC, Lira SA, Parkhurst CN, Garambois V, Brengues M, Tadokoro CE, Trimarchi T, Gómez-López G, Singh A, Khiabanian H, Minuzzo S, Indraccolo S, Lobry C, Aifantis I, Herranz D, Lafaille JJ, Maraver A. Xiong H, et al. Theranostics. 2021 Jan 1;11(4):1594-1608. doi: 10.7150/thno.48067. eCollection 2021. Theranostics. 2021. PMID: 33408769 Free PMC article.
• Notch1 Drives the Formation and Proliferation of Intrahepatic Cholangiocarcinoma.
  Guo J, Fu W, Xiang M, Zhang Y, Zhou K, Xu CR, Li L, Kuang D, Ye F. Guo J, et al. Curr Med Sci. 2019 Dec;39(6):929-937. doi: 10.1007/s11596-019-2125-0. Epub 2019 Dec 16. Curr Med Sci. 2019. PMID: 31845224

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science
  • Silverchair Information Systems

• Other Literature Sources

  • The Lens - Patent Citations

• Molecular Biology Databases

  • Mouse Genome Informatics (MGI)

• Research Materials

  • NCI CPTC Antibody Characterization Program