Capitalizing on the activation of NOXA, the combination of the SPHK1 inhibitor with venetoclax (a BH3 mimetic and inhibitor of BCL2) was shown to synergize and overcome resistance of OCI-AML3, an intrisically venetoclax-resistant cell line and in AML patient samples with mutations linked to venetoclax resistance (both in vitro and in in vivo AML PDXs) and in Leukemic Stem Cells [142]. The gene discussed is PMAIP1; the disease is acute myeloid leukemia.