MYB down-regulation enhances sensitivity of U937 myeloid leukemia cells to the histone deacetylase inhibitor LBH589 in vitro and in vivo

• Inducible shRNA-mediated MYB knockdown suppresses growth of U937 leukaemia cells in vitro and in vivo.
• MYB knockdown sensitises U937 cells to apoptosis induction by LBH-589 in vitro.
• MYB knockdown combined with low-dose LBH-589 enhances suppression of leukaemia development.
• Derepression of pro-apoptotic BCL2 family members may mediate apoptosis by the combined treatment.

The effect of combining MYB suppression with the histone deacetylase inhibitor LBH589 was studied in human myeloid leukemia cell lines. MYB knockdown inhibited proliferation and induced apoptosis in U937 and K562 cells in vitro, and also sensitized both to the pro-apoptotic effect of LBH589. This was accompanied by enhanced expression of the pro-apoptotic BCL2 family members BOK and BIM. U937 cells carrying inducible MYB shRNA were also transplanted into NOD/SCID mice. The combination of MYB knockdown and LBH589 prolonged survival compared to either treatment alone, suggesting that further development of such combinations might lead to effective and safe leukemia therapies.