The hypoxia signalling pathway in haematological malignancies

Oncotarget. 2017 May 30;8(22):36832-36844. doi: 10.18632/oncotarget.15981.

Abstract

Haematological malignancies are tumours that affect the haematopoietic and the lymphatic systems. Despite the huge efforts to eradicate these tumours, the percentage of patients suffering resistance to therapies and relapse still remains significant. The tumour environment favours drug resistance of cancer cells, and particularly of cancer stem/initiating cells. Hypoxia promotes aggressiveness, metastatic spread and relapse in most of the solid tumours. Furthermore, hypoxia is associated with worse prognosis and resistance to conventional treatments through activation of the hypoxia-inducible factors. Haematological malignancies are not considered solid tumours, and therefore, the role of hypoxia in these diseases was initially presumed to be inconsequential. However, hypoxia is a hallmark of the haematopoietic niche. Here, we will review the current understanding of the role of both hypoxia and hypoxia-inducible factors in different haematological tumours.

Keywords: cancer stem cells; haematological cancers; hypoxia; hypoxia-inducible factors; resistance.

Publication types

  • Review

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / antagonists & inhibitors
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Bone Marrow / metabolism
  • Bone Marrow / pathology
  • Cell Hypoxia
  • Hematologic Neoplasms / drug therapy
  • Hematologic Neoplasms / etiology
  • Hematologic Neoplasms / metabolism*
  • Hematologic Neoplasms / pathology
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Hypoxia / genetics
  • Hypoxia / metabolism*
  • Molecular Targeted Therapy
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Signal Transduction* / drug effects
  • Stem Cell Niche
  • Stromal Cells / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors