The BCR-ABL/NF-κB signal transduction network: a long lasting relationship in Philadelphia positive Leukemias

Oncotarget. 2016 Oct 4;7(40):66287-66298. doi: 10.18632/oncotarget.11507.

Abstract

The Nuclear Factor-kappa B (NF-κB) family of transcription factors plays a key role in cancer pathogenesis due to the ability to promote cellular proliferation and survival, to induce resistance to chemotherapy and to mediate invasion and metastasis. NF-κB is recruited through different mechanisms involving either canonical (RelA/p50) or non-canonical pathways (RelB/p50 or RelB/p52), which transduce the signals originated from growth-factors, cytokines, oncogenic stress and DNA damage, bacterial and viral products or other stimuli. The pharmacological inhibition of the NF-κB pathway has clearly been associated with significant clinical activity in different cancers. Almost 20 years ago, NF-κB was described as an essential modulator of BCR-ABL signaling in Chronic Myeloid Leukemia and Philadelphia-positive Acute Lymphoblastic Leukemia. This review summarizes the role of NF-κB in BCR-ABL-mediated leukemogenesis and provides new insights on the long lasting BCR-ABL/NF-κB connection.

Keywords: BCR-ABL; CML; IκB-α; NF-κB; NFKBIA.

Publication types

  • Review

MeSH terms

  • Apoptosis
  • Cell Proliferation
  • Fusion Proteins, bcr-abl / metabolism*
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
  • NF-kappa B / metabolism*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology*
  • Signal Transduction

Substances

  • NF-kappa B
  • Fusion Proteins, bcr-abl