Targeting the bone marrow microenvironment in acute leukemia

Abstract

Despite individual differences between certain leukemias, the overall survival rate in acute leukemia remains low at approximately 40%. Novel therapeutics, including targeted therapies like tyrosine kinase inhibitors, have been incorporated into treatment regimens, but most have failed at eradicating leukemic stem cells (LSCs). The causes of disease relapse, progression, and resistance to chemotherapy are as yet not entirely clear but thought to be linked to protection in the bone marrow microenvironment (BMM). In this review, we summarize current knowledge on the BMM in acute leukemias and examine the ongoing efforts to target the BMM, which include treatment strategies targeting (a) leukemia–BMM interactions, (b) leukemia–cell intrinsic pathways influenced by the BMM, and (c) direct BMM targeting strategies. It is likely that the future ploy against leukemia will involve these and other innovative strategies designed to eradicate the last remaining warrior – the LSC.

Keywords:

• Bone marrow microenvironment
• acute leukemia
• niche targeting drugs

Acknowledgements

This work was supported by the LOEWE Center for Cell and Gene Therapy Frankfurt (CGT), as well as the LOEWE Program Ub Net.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2018.1434886.