In the context of AML, S1P signaling is central to the initiation of leukemia, where overexpression of S1PR3 leads to leukemogenesis.181 The S1P-S1PR3 axis has also been found to initiate the inflammatory program and myeloid cell differentiation bias among leukemic stem cells (LSCs) from AML patients, which express high levels of S1PR3. Here, S1PR3 is linked to leukemia.