Could AML Progression Be Fueled by Chemotherapy-Induced Dormancy of AML Cells?
Posted: Friday, March 12, 2021
According to research presented in Cancer Discovery, acute myeloid leukemia (AML) cells may enter a senescence-like dormant phase following chemotherapy, allowing for eventual disease reemergence and relapse. This phase was previously thought to be a terminal stage of halted cell growth and division.
“We observed that after a certain number of weeks the AML cells escaped senescence,” noted Cihangir Duy, PhD, MS, of Fox Chase Cancer Center, in an institutional press release. “Our study suggests there are conserved resilience mechanisms in cells to cope with environmental challenges. AML cells take advantage of these conserved resilience mechanisms to survive chemotherapy.”
The investigators conducted in vitro and in vivo analyses to determine the mechanism that supports AML reemergence following chemotherapy, which commonly occurs. Patient-derived cells were treated with chemotherapy and then monitored for their response. Though many cells died, some survived. There did not appear to be a correlation between survival and categorization as a leukemia stem cell. The remaining cells were large and did not experience further growth. Long-term monitoring of these cells revealed that, upon recovery, they have an increased stem cell potential, which contributes to disease relapse.
Activation of the cellular resilience mechanism was found to be dependent on the ataxia telangiectasia and Rad3-related (ATR) protein kinase, a critical moderator of cellular DNA damage response. Inhibition of the ATR protein kinase impaired the persistence of AML cells. The study suggests that ATR inhibitors may be an option for targeted treatment following chemotherapy.
Disclosure: For full disclosures of the study authors, visit cancerdiscovery.aacrjournals.org.