The role of microenvironment and immunity in drug response in leukemia

Biochim Biophys Acta. 2016 Mar;1863(3):414-426. doi: 10.1016/j.bbamcr.2015.08.003. Epub 2015 Aug 6.

Abstract

Leukemia is a cancer of the white blood cells, with over 54,000 new cases per year diagnosed worldwide and a 5-year survival rate below 60%. This highlights a need for research into the mechanisms behind its etiology and causes of therapy failure. The bone marrow microenvironment, in which adult stem cells are maintained in healthy individuals, has been implicated as a source of chemoresistance and disease relapse. Here the various ways that the microenvironment can contribute to the resistance and persistence of leukemia are discussed. The targeting of the microenvironment by leukemia cells to create an environment more suitable for cancer progression is described. The role of soluble factors, drug transporters, microvesicles, as well as the importance of direct cell-cell contact, in addition to the effects of inflammation and immune surveillance in microenvironment-mediated drug resistance are discussed. An overview of the clinical potential of translating research findings to patients is also provided. Understanding of and further research into the role of the bone marrow microenvironment in leukemia progression and relapse are crucial towards developing more effective treatments and reduction in patient morbidity. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza.

Keywords: Cancer; Immune surveillance; Inflammation; Leukemia; Microenvironment; Novel therapeutics.

Publication types

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

MeSH terms

  • Antineoplastic Agents / classification
  • Antineoplastic Agents / immunology
  • Antineoplastic Agents / therapeutic use*
  • Bone Marrow / drug effects*
  • Bone Marrow / immunology
  • Bone Marrow / pathology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / pathology
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / immunology
  • Humans
  • Immunity / drug effects*
  • Leukemia / drug therapy*
  • Leukemia / immunology
  • Models, Immunological
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / immunology
  • Neoplastic Stem Cells / pathology
  • Tumor Microenvironment / drug effects*
  • Tumor Microenvironment / immunology

Substances

  • Antineoplastic Agents