Shedding Light on Treatment-Resistant Leukemia Stem Cells
Posted: Friday, April 5, 2019
Although tyrosine kinase inhibitors are effective in the treatment of chronic myeloid leukemia (CML), they do not “eliminate disease-propagating leukemic stem cells, suggesting a deeper understanding of niche-dependent regulation of CML leukemia stem cells is required to eradicate disease.” These words are from Ravi Bhatia, MD, and colleagues at the University of Alabama at Birmingham (UAB), who studied the chemokine CXCL12 and how its niche-specific expression may play a role in treatment resistance. Their research findings were published in Cell Stem Cell.
“This work identifies the specific mesenchymal stromal cell niche cells that are responsible for maintaining leukemic stem cells in a quiescent and treatment-resistant state and indicates that targeting these niche interactions can activate leukemia stem cells,” stated Dr. Bhatia in a UAB press release. As a result, he continued, these leukemia stem cells may become sensitive to treatment.
The UAB researchers, along with international colleagues, conducted bone marrow imaging studies, which revealed that stromal cells reorganized to co-localize with leukemia stem cells in discrete regions in the bone marrow. With targeted deletion of CXCL12, these regions of co-localized mesenchymal stromal and leukemia stem cells were lost. The investigators also found that the increased self-renewing divisions of the leukemia stem cells may be related to enhanced activity of the EZH2 gene. And, in mice, the loss of CXCL12 expression in endothelial cells of the bone marrow microenvironment resulted in a decrease in the number of CML stem cells, thereby extending the rate of survival.
Disclosure: The study authors’ disclosure information can be found at cell.com.