PI3Kδ Inhibitor Idelalisib Inhibits AKT Signaling In Myelofibrosis Patients On Chronic JAK Inhibitor Therapy
Meadows S, Nguyen H, Queva C et al.




Key Points:
  • PI3K inhibitor idelalisib efficacious in patients with CLL and indolent NHL.

  • Investigated whether PI3Kδ isoform expressed in progenitor cells from MF patients, and also evaluated inhibitory effects of idelalisib on cell lines and primary cells from MF patients.

  • Used CD34+ cells from the peripheral blood of MF patients as well as cell lines and then incubated with idelalisib.

  • Predominant PKI isoform δ-isoform; PI3Kβ expressed at lower levels and no PI3Kα or γ detected.

  • Treatment of BaF3/MPL cells with idelalisib decreased the levels of p-AKT by 51%, 64% and 67%, with 0.1, 1.0, 2.0 µM , respectively, when compared to idelalisib-untreated cells.

Implications:

  • PI3K-δ predominant isoform expressed in CD34+ cells from MF patients.

  • In both cell lines, idelalisib inhibits the PI3K/AKT pathway.


View the original abstract on the ASH website.






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