ACUTE MYELOID LEUKEMIA THERAPY
Acute myeloid leukemia (AML) is an aggressive cancer of the blood, where malignant myeloid blasts accumulate in the bone marrow. One of the challenges of effective AML treatment is resistance to cytarabine (or ara-C), a standard AML chemotherapeutic drug used in front-line treatment today (Nair et al., 2021).
In 2017, Schneider et al. reported the dNTPase sterile alpha motif and HD-domain-containing protein 1 (SAMHD1) to be a targetable biomarker for ara-C treatment response (Schneider, Oellerich, Baldauf et al., 2017). The intracellular triphosphorylated active form of ara-C, ara-CTP, is recognized as a substrate by SAMHD1, which leads to a decrease in the amount of ara-CTP within the cells and consequently reduced cytotoxicity (Schneider, Oellerich, Baldauf et al. 2017).
SAMHD1 can be targeted by the lentiviral accessory protein Vpx for proteasomal degradation by interacting with the proteasomal degradation complex and SAMHD1. We in the VIIRAL lab aim to use Vpx to target SAMHD1 in AML cells to improve ara-C sensitivity.
Graphical summary of novel insights into pathways that contribute to the survival of AML cells. One of the ways AML cells can evade drug-induced cytotoxicity is via the activity of SAMHD1. (Nair et al., 2021)
Key publications on this topic
Nair et al.
Journal: Analytical Biochemistry
Nair et al.
Rothenburger T, Baldauf HM, et al.
Journal: Journal of Experimental & Clinical Cancer Research
Schneider, Oellerich, Baldauf et al.
Journal: Nature Medicine
Photo by Maik Richter