All content on this site is intended for healthcare professionals only. By acknowledging this message and accessing the information on this website you are confirming that you are a Healthcare Professional. If you are a patient or carer, please visit Know AML.
Introducing
Now you can personalise
your AML Hub experience!
Bookmark content to read later
Select your specific areas of interest
View content recommended for you
Find out moreThe AML Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the AML Hub cannot guarantee the accuracy of translated content. The AML Hub and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.
Bookmark this article
Artemisinins are a family of antimalarial compounds whose activity is facilitated by the generation of Reactive Oxygen Species (ROS).
The antineoplastic activity and mechanism of action of artemisinins, in particular Artesunate (ARTS), in Acute Myeloid Leukemia (AML) was investigated by Bijender Kumar and colleagues from City of Hope Medical Center, Duarte, CA, USA. The results were published in Leukemia Research on 12th May 2017.
Using Fms Like Tyrosine Kinase 3 – Internal Tandem Duplication (FLT3-ITD) positive AML cell lines, MV4-11 and MOLM-13, the authors investigated the anti-proliferative activity and cytotoxicity of ARTS in vitro.
The authors also investigated the in vivo activity of ARTS in an AML mouse model.
In summary, ARTS has a potent antileukemic activity in AML, which is mediated by the induction of ROS. Additionally, ARTS augments the cytotoxicity of chemotherapy and ABT-199.
The authors concluded by suggesting that their results support the use of ARTS in combination with standard chemotherapy or venetoclax in clinical studies in patients with AML.
The artimisinins are a class of antimalarial compounds whose antiparasitic activity is mediated by induction of reactive oxygen species (ROS). Herein, we report that among the artimisinins, artesunate (ARTS), an orally bioavailable compound has the most potent antileukemic activity in AML models and primary patients’ blasts. ARTS was most cytotoxic to the FLT3-ITD+ AML MV4-11 and MOLM-13 cells (IC50 values of 1.1 and 0.82 μM respectively), inhibited colony formation in primary AML and MDS cells and augmented cytotoxicity of chemotherapeutics. ARTS lowered cellular BCL-2 level via ROS induction and increased the cytotoxicity of the BCL-2 inhibitor venetoclax (ABT-199). ARTS treatment led to cellular and mitochondrial ROS accumulation, double stranded DNA damage, loss of mitochondrial membrane potential and induction of the intrinsic mitochondrial apoptotic cascade in AML cell lines. The antileukemic activity of ARTS was further confirmed in MV4-11 and FLT3-ITD+ primary AML cell xenografts as well as MLL-AF9 syngeneic murine AML model where ARTS treatment resulted in significant survival prolongation of treated mice (P = 0.012 for the FLT3-ITD xenograft model) compared to control. Our results demonstrate the potent preclinical antileukemic activity of ARTS as well as its potential for a rapid transition to a clinical trial either alone or in combination with conventional chemotherapy or BCL-2 inhibitor, for treatment of AML.
Your opinion matters
Subscribe to get the best content related to AML delivered to your inbox