Targeting the bone marrow microenvironment in acute leukemia
- 12 February 2018
- journal article
- review article
- Published by Informa UK Limited in Leukemia & Lymphoma
- Vol. 59 (11), 2535-2545
- https://doi.org/10.1080/10428194.2018.1434886
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
This publication has 82 references indexed in Scilit:
- Endothelial and perivascular cells maintain haematopoietic stem cellsNature, 2012
- Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell nicheThe Journal of Experimental Medicine, 2011
- High levels of the adhesion molecule CD44 on leukemic cells generate acute myeloid leukemia relapse after withdrawal of the initial transforming eventLeukemia, 2010
- Mesenchymal and haematopoietic stem cells form a unique bone marrow nicheNature, 2010
- Bone progenitor dysfunction induces myelodysplasia and secondary leukaemiaNature, 2010
- Endothelial progenitor cell infusion induces hematopoietic stem cell reconstitution in vivoBlood, 2009
- Very late antigen-4 function of myeloblasts correlates with improved overall survival for patients with acute myeloid leukemiaBlood, 2009
- A Microenvironment-Induced Myeloproliferative Syndrome Caused by Retinoic Acid Receptor γ DeficiencyCell, 2007
- Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxiaProceedings of the National Academy of Sciences of the United States of America, 2007
- The stem cell niches in boneJCI Insight, 2006