Moreover, even though 64% of already venetoclax resistant cells were able to survive to a second drug exposure, 50% of these cells died due to the presence of venetoclax in combination with SKI-II and 75% in combination with opaganib, showing that SPHK inhibitors were able to re-sensitize resistant CLL cells to a second venetoclax treatment (Figure 4E). This evidence concerns the gene SPHK1 and B-cell chronic lymphocytic leukemia.