Abstract
Treatment of 32 acute myeloid leukemia (AML) blast samples showing activation of the PI3K and RAS/RAF/MEK/ERK pathways with the PI3K p110δ isoform and MEKinase selective inhibitors, PCN5603 and U0126 produced dose dependent progenitor kill and inhibition of p-Akt Ser473 and p-Erk Tyr204 expression. Normal marrow or blood progenitors were less sensitive to these inhibitors (median PCN5603 IC50s for AML and normal cells 1.5 and 5.8μM and for U0126 9.6 and 25.8μM, respectively). U0126 synergized with PCN5603 for killing of both AML and normal progenitors. However, the synergy was less for normal than for AML cells and the median IC50 of each drug in the combination 7- to 10-fold higher than for AML cells.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
