Establishment of a novel B-cell lymphoma cell line with suppressed growth by gamma-secretase inhibitors

Leuk Res. 2006 Nov;30(11):1385-90. doi: 10.1016/j.leukres.2006.05.003. Epub 2006 Jun 14.

Abstract

A novel lymphoma cell line, designated TMD8 was established from cells of a patient with diffuse large B-cell lymphoma. TMD8 cells expressed HES1 mRNA, suggesting constitutive activation of Notch signaling. TMD8 cells expressed normal-sized Notch1 protein, and showed no mutations in the NOTCH1 gene. Cell growth was suppressed by gamma-secretase inhibitors (GSI). It was reported that GSI suppressed growth of T-cell acute lymphoblastic leukemia (T-ALL) cell lines, which frequently had NOTCH1 mutations. In addition to T-ALL, TMD8 is another unique cell line sensitive to GSI, and is useful to study effects of GSI in molecular targeting therapy.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid Precursor Protein Secretases / antagonists & inhibitors*
  • Basic Helix-Loop-Helix Transcription Factors / drug effects
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Cell Line, Tumor*
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Dipeptides / pharmacology*
  • Enzyme Inhibitors / pharmacology*
  • Fatal Outcome
  • Homeodomain Proteins / drug effects
  • Homeodomain Proteins / genetics
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Jagged-2 Protein
  • Karyotyping
  • Ligands
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / pathology*
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Oligopeptides / pharmacology*
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • Receptor, Notch1 / genetics
  • Receptor, Notch2 / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Structure-Activity Relationship
  • Transcription Factor HES-1

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DLL4 protein, human
  • Dipeptides
  • Enzyme Inhibitors
  • Homeodomain Proteins
  • Intercellular Signaling Peptides and Proteins
  • JAG2 protein, human
  • Jagged-2 Protein
  • Ligands
  • Membrane Proteins
  • N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester
  • NOTCH1 protein, human
  • NOTCH2 protein, human
  • Oligopeptides
  • RNA, Messenger
  • Receptor, Notch1
  • Receptor, Notch2
  • Transcription Factor HES-1
  • benzyloxycarbonyl-isoleucyl-leucinal
  • benzyloxycarbonyl-leucyl-leucyl-norleucinal
  • HES1 protein, human
  • Amyloid Precursor Protein Secretases