The sensitivity of chronic myeloid leukemia CD34 cells to Bcr-Abl tyrosine kinase inhibitors is modulated by ceramide levels

Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies

“…The sphingolipidomics profile was also recently analyzed in plasma from patients at different stages of CML, including TKI-resistant patients, and it was found that ceramide levels were increased in TKI-resistant patients while SM and S1P levels were decreased in the chronic- and accelerated-phase CML [ 255 ]. These results seem to be discordant from sphingolipid levels measured in primary cells, particularly in the case of TKI resistance and this might be due to measurements in plasma versus cells [ 254 ].…”

“…Analysis of SL levels in CD34 + cells derived from the bone marrow of patients who have advanced to the aggressive and refractory blast-phase of CML showed that ceramide levels in leukemic CD34 + cells were significantly lower than in normal CD34 + cells. The extent of ceramide reduction in blast-phase CML cells correlated with the level of resistance to TKIs [ 254 ]. Apoptosis of multiple CML cell lines including blast-phase CML CD34 + cells was achieved by increasing ceramide level with the addition of the short chain ceramide analog C2-ceramide or pharmacological inhibition of ceramide metabolizing enzymes with PDMP and SKI-II [ 197 ].…”

“…Synergistic effects against blast-phase CML progenitor cells were observed with a combination of dasatinib or nilotinib with either C2-ceramide or PDMP and SKI-II. Thus, the elevation of ceramide induced apoptosis and rescued sensitivity to TKIs [ 254 ]. The sphingolipidomics profile was also recently analyzed in plasma from patients at different stages of CML, including TKI-resistant patients, and it was found that ceramide levels were increased in TKI-resistant patients while SM and S1P levels were decreased in the chronic- and accelerated-phase CML [ 255 ].…”