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).

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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).

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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.