Abstract
BackgroundDormant chemotherapy-resistant leukemia cells can survive for an extended period before relapse. Nevertheless, the mechanisms underlying the development of chemoresistance in vivo remain unclear.MethodsUsing intravital bone imaging, we characterized the behavior of murine acute myeloid leukemia (AML) cells (C1498) in the bone marrow before and after chemotherapy with cytarabine.ResultsProliferative C1498 cells exhibited high motility in the bone marrow. Cytarabine treatment impaired the motility of residual C1498 cells. However, C1498 cells regained their migration potential after relapse. RNA sequencing revealed that cytarabine treatment promoted MRTF-SRF pathway activation. MRTF inhibition using CCG-203971 augmented the anti-tumor effects of chemotherapy in our AML mouse model, as well as suppressed the migration of chemoresistant C1498 cells.ConclusionsThese results provide novel insight into the role of cell migration arrest on the development of chemoresistance in AML, as well as provide a strong rationale for the modulation of cellular motility as a therapeutic target for refractory AML.
Highlights
Dormant chemotherapy-resistant leukemia cells can survive for an extended period before relapse
C1498 cells were fluorescently labeled with green fluorescent protein (GFP) by retroviral transduction, allowing for tracking of the engrafted acute myeloid leukemia (AML) cells
We hypothesized that the development of chemoresistance in AML cells is accompanied by changes in cell motility; we analyzed the dynamics of chemoresistant AML cells in the bone marrow (BM) following cytarabine treatment
Summary
Dormant chemotherapy-resistant leukemia cells can survive for an extended period before relapse. The mechanisms underlying the development of chemoresistance in vivo remain unclear. Another study suggested that AML cell migration did not depend on interactions with ligands found in the BM stroma [7]. These contradictive findings highlight the complexity of the mechanisms underlying the interactions between AML cells and BM microenvironment components. Characterization of the exact localization and Morimatsu et al Inflammation and Regeneration (2020) 40:15 movements of chemotherapy-resistant AML cells within the BM is of high importance for a better understanding of the mechanisms underlying resistance
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
