SYK Inhibition Modulates Distinct PI3K/AKT- Dependent Survival Pathways and Cholesterol Biosynthesis in Diffuse Large B Cell Lymphomas Academic Article uri icon

Overview

MeSH Major

  • Intracellular Signaling Peptides and Proteins
  • Lymphoma, Large B-Cell, Diffuse
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-bcr

abstract

  • B cell receptor (BCR) signaling pathway components represent promising treatment targets in diffuse large B cell lymphoma (DLBCL) and additional B cell tumors. BCR signaling activates spleen tyrosine kinase (SYK) and downstream pathways including PI3K/AKT and NF-κB. In previous studies, chemical SYK blockade selectively decreased BCR signaling and induced apoptosis of BCR-dependent DLBCLs. Herein, we characterize distinct SYK/PI3K-dependent survival pathways in DLBCLs with high or low baseline NF-κB activity including selective repression of the pro-apoptotic HRK protein in NF-κB-low tumors. We also define SYK/PI3K-dependent cholesterol biosynthesis as a feed-forward mechanism of maintaining the integrity of BCRs in lipid rafts in DLBCLs with low or high NF-κB. In addition, SYK amplification and PTEN deletion are identified as selective genetic alterations in primary "BCR"-type DLBCLs.

publication date

  • June 10, 2013

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3700321

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2013.05.002

PubMed ID

  • 23764004

Additional Document Info

start page

  • 826

end page

  • 38

volume

  • 23

number

  • 6