Our early studies in AML suggested S1P may have a pro-survival function in AML CSC, since SPHK1 inhibition induced degradation of MCL1, a key pro-survival protein in AML, resulting in death of isolated AML stem and progenitor cells, and reduced tumour burden in AML patient-derived xenografts in mice [65]. This evidence concerns the gene MCL1 and acute myeloid leukemia.