Selenium-dependent cyclopentanone prostaglandin (CyPG) production can induce leukemia-protective effects in chronic myeloid leukemia by CyPG activation of PPARγ, which initiates leukemic stem cell (LSC) death; it is suspected that CyPGs can also inhibit LSCs by activation of Gpr44 to induce apoptosis. A novel LSC eradication therapy to suppress disease severity and relapse potential was investigated with CyPG treatment and Gpr44 gene inactivation studies to determine roles of Gpr44 in an experimental model of CML.