RUNX1/ETO regulates reactive oxygen species (ROS) levels in t(8,21) acute myeloid leukaemia via FLT3 and RAC1.
Adam AzlanKang Zi KhorYaashini RajasegaranAliaa Arina RosliMohamed Saifulaman Mohamed SaidNarazah Mohd YusoffEmmanuel Jairaj MosesPublished in: Medical oncology (Northwood, London, England) (2023)
Reactive oxygen species (ROS) homeostasis is crucial for leukaemogenesisand deregulation would hamper leukaemic progression. Although the regulatory effects of RUNX1/ETO has been extensively studied, its underlying molecular mechanims in ROS production in t(8,21) AML is yet to be fully elucidated. Here, we report that RUNX1/ETO could directly control FLT3 by occupying several DNA elements on FLT3 locus. The possible hijacking mechanism by RUNX1/ETO over FLT3 mediated ROS modulation in AML t(8;21) was made apparent when suppression of RUNX1/ETO led to decrement in ROS levels and the direct oxidative marker FOXO3 but not in FLT3 and RAC1 suppressed t(8,21) AML cell line Furthermore, nuclear import of RUNX1/ETO was aberrated following RUNX1/ETO and RAC1 suppression suggesting association in ROS control. A different picture was depicted in non t(8;21) cells where suppression of RAC1 and FLT3 led to decreased levels of FOXO3a and ROS. Results alltogether indicate a possible dysregulation of ROS levels by RUNX1/ETO in t(8,21) AML.
Keyphrases
- acute myeloid leukemia
- reactive oxygen species
- transcription factor
- cell death
- dna damage
- allogeneic hematopoietic stem cell transplantation
- tyrosine kinase
- intensive care unit
- bone marrow
- computed tomography
- dendritic cells
- signaling pathway
- immune response
- oxidative stress
- single molecule
- circulating tumor cells