Asparaginase unveils glutamine-addicted AML

Abstract

In this issue of Blood, Willems et al describe the dependence of acute myeloid leukemia (AML) cells on glutamine for maintaining protein synthesis downstream of mammalian target of rapamycin (mTOR) and show that the enzyme asparaginase can be used to target this dependence. Using various AML cell lines, primary samples, and CD341 stem cells from healthy donors, the authors support the notion that asparaginase may offer a therapeutic benefit in AML—not from its well-known enzymatic activity, but from its “off-target” effects on glutamine levels that result in inhibition of downstream mTOR signaling, inhibition of protein synthesis, and ultimately loss of viability.