MYB down-regulation enhances sensitivity of U937 myeloid leukemia cells to the histone deacetylase inhibitor LBH589 in vitro and in vivo.
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.
School of Pharmacy, The University of Queensland, Brisbane, Queensland 4102, Australia; The University of Queensland Diamantina Institute, Brisbane, Queensland 4102, Australia.
Ping
P
Ye
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Liang
L
Zhao
School of Pharmacy, The University of Queensland, Brisbane, Queensland 4102, Australia; The University of Queensland Diamantina Institute, Brisbane, Queensland 4102, Australia.
Crystal
C
McGirr
School of Pharmacy, The University of Queensland, Brisbane, Queensland 4102, Australia; The University of Queensland Diamantina Institute, Brisbane, Queensland 4102, Australia. Electronic address: t.gonda@uq.edu.au.
Thomas J
TJ
Gonda
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry; D017209:Apoptosis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002470:Cell Survival; D015972:Gene Expression Regulation, Neoplastic; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D020014:K562 Cells; D015470:Leukemia, Myeloid, Acute / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D000077767:Panobinostat; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism*; D034622:RNA Interference; D020298:U937 Cells
D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D020598:Proto-Oncogene Proteins c-myb; D000077767:Panobinostat
AML; Apoptosis; LBH589/Panobinostat; MYB; Xenograft