Published online Aug 26, 2019. doi: 10.4252/wjsc.v11.i8.476
Peer-review started: March 15, 2019
First decision: June 4, 2019
Revised: June 13, 2019
Accepted: June 20, 2019
Article in press: June 20, 2019
Published online: August 26, 2019
Processing time: 167 Days and 19.2 Hours
Bone marrow microenvironment (BMM) is the main sanctuary of leukemic stem cells (LSCs) and protects these cells against conventional therapies. However, it may open up an opportunity to target LSCs by breaking the close connection between LSCs and the BMM. The elimination of LSCs is of high importance, since they follow cancer stem cell theory as a part of this population. Based on cancer stem cell theory, a cell with stem cell-like features stands at the apex of the hierarchy and produces a heterogeneous population and governs the disease. Secretion of cytokines, chemokines, and extracellular vesicles, whether through autocrine or paracrine mechanisms by activation of downstream signaling pathways in LSCs, favors their persistence and makes the BMM less hospitable for normal stem cells. While all details about the interactions of the BMM and LSCs remain to be elucidated, some clinical trials have been designed to limit these reciprocal interactions to cure leukemia more effectively. In this review, we focus on chronic myeloid leukemia and acute myeloid leukemia LSCs and their milieu in the bone marrow, how to segregate them from the normal compartment, and finally the possible ways to eliminate these cells.
Core tip: Chronic myeloid leukemia stem cells (LSCs) and acute myeloid LSCs are resistant to common therapies due to the activation of downstream signaling pathways that guarantee their survival. In addition, they are smart enough to escape immune surveillance. Bone marrow microenvironment underlies these phenomena by providing an environment that favors leukemia development. Recent studies confirm that targeting LSCs and their crosstalk with the bone marrow microenvironment significantly reduced residual disease burden and eventuated in LSCs removal.