The role of microenvironment and immunity in drug response in leukemia

Bakker, EY; Qattan, M; Mutti, L; Demonacos, C; Krstic- Demonacos, M

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.

• Journal Article Type: Article
• Acceptance Date: Aug 1, 2015
• Online Publication Date: Aug 6, 2015
• Publication Date: Aug 6, 2015
• Deposit Date: Sep 18, 2015
• Publicly Available Date: Apr 5, 2016
• Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
• Print ISSN: 0167-4889
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 1863
• Issue: 3
• Pages: 414-426
• DOI: https://doi.org/10.1016/j.bbamcr.2015.08.003
• Publisher URL: http://dx.doi.org/10.1016/j.bbamcr.2015.08.003
• Related Public URLs: https://www.journals.elsevier.com/bba-molecular-cell-research
• Additional Information: Projects : Please note that this project is funded by above mentioned Universities. GIMe is a charity that supports research by Professor Mutti.