SPHK2 and chronic myelogenous leukemia, BCR-ABL1 positive: In addition, the SK1/S1P/S1PR2 signaling pathway leads to imatinib resistance in chronic myeloid leukemia (CML) [37], and the SK2/S1P/S1PR1/S1PR3 signaling pathway renders the A549 lung cancer cell line resistant to etoposide [38].