Sterile α motif and histidine/aspartic acid domain containing protein 1 (SAMHD1) is a deoxynucleoside triphosphate (dNTPs) triphosphohydrolase that can hydrolyze dNTPs into deoxynucleosides and triphosphates to keep the balance of the intracellular dNTPs pool. Moreover

it has been reported that SAMHD1 plays a role in regulating cell proliferation and the cell cycle

maintaining genome stability and inhibiting innate immune responses. SAMHD1 activity is regulated by phosphorylation

oxidation

SUMOylation

and O-GlcNAcylation. SAMHD1 mutations have been reported to cause diseases

including chronic lymphocytic leukemia and mantle cell lymphoma. SAMHD1 expression in acute myeloid leukemia predicts inferior prognosis. Recently

it has been revealed that SAMHD1 mediates the resistance to anti-cancer drugs. This review will focus on SAMHD1 function and regulation

the association between SAMHD1 and hematological malignancies and will provide updated information on SAMHD1 mediating resistance to nucleoside analogue antimetabolites

topoisomerase inhibitors

platinum-derived agents and DNA hypomethylating agents. Furthermore

histone deacetylase inhibitors and tyrosine kinase inhibitors indirectly increase anti-cancer drug resistance by increasing SAMDH1 activity. We herein highlight the importance of the development of novel agents targeting SAMHD1 to overcome treatment resistance of hematological malignancies

which would be an opportunity to improve the outcome of patients with refractory hematological malignancies.