Cotreatment with LBH589 and/or 1.7-AAG-induces more loss of cell viability than either agent alone in primary AML or CML-BC cells.
. | . | Cell death, % . | . | . | . | . | . | . | . | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | . | nM, 17-AAG . | . | nM, LBH589 . | . | 10 nM, LBH589 + nM, 17-AAG . | . | 50 nM, LBH589 + nM, 17-AAG . | . | |||||||
Patient no. . | Control . | 250 . | 1000 . | 10 . | 50 . | 250 . | 1000 . | 250 . | 1000 . | |||||||
CML-BC cells | ||||||||||||||||
1 | 2.1 | 2.8 | 9.1 | 12.9 | 37.0 | 42.3 | 49.0 | 55.7 | 59.3 | |||||||
2 | 4.5 | 9.6 | 38.0 | 38.5 | 56.0 | 48.5 | 63.8 | 63.0 | 74.0 | |||||||
3 | 4.0 | 5.8 | 21.0 | 16.4 | 19.9 | 53.0 | 63.0 | 61.5 | 76.0 | |||||||
4 | 10.1 | 16.9 | 24.1 | 18.8 | 28.0 | 30.0 | 38.8 | 39.8 | 42.4 | |||||||
5 | 9.3 | 15.8 | 26.3 | 22.7 | 44.9 | 33.1 | 49.1 | 44.7 | 50.3 | |||||||
AML cells | ||||||||||||||||
1 | 5.6 | 12.2 | 43.7 | 17.4 | 45.8 | 46.5 | 58.9 | 63.3 | 66.2 | |||||||
2 | 13.1 | 28.5 | 58.1 | 34.7 | 55.9 | 54.3 | 71.6 | 63.6 | 73.2 | |||||||
3 | 7.6 | 21.7 | 39.1 | 19.6 | 39.7 | 44.1 | 53.7 | 60.9 | 67.2 | |||||||
4 | 9.4 | 26.3 | 46.4 | 31.3 | 51.4 | 57.6 | 69.4 | 75.6 | 79.1 |
. | . | Cell death, % . | . | . | . | . | . | . | . | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | . | nM, 17-AAG . | . | nM, LBH589 . | . | 10 nM, LBH589 + nM, 17-AAG . | . | 50 nM, LBH589 + nM, 17-AAG . | . | |||||||
Patient no. . | Control . | 250 . | 1000 . | 10 . | 50 . | 250 . | 1000 . | 250 . | 1000 . | |||||||
CML-BC cells | ||||||||||||||||
1 | 2.1 | 2.8 | 9.1 | 12.9 | 37.0 | 42.3 | 49.0 | 55.7 | 59.3 | |||||||
2 | 4.5 | 9.6 | 38.0 | 38.5 | 56.0 | 48.5 | 63.8 | 63.0 | 74.0 | |||||||
3 | 4.0 | 5.8 | 21.0 | 16.4 | 19.9 | 53.0 | 63.0 | 61.5 | 76.0 | |||||||
4 | 10.1 | 16.9 | 24.1 | 18.8 | 28.0 | 30.0 | 38.8 | 39.8 | 42.4 | |||||||
5 | 9.3 | 15.8 | 26.3 | 22.7 | 44.9 | 33.1 | 49.1 | 44.7 | 50.3 | |||||||
AML cells | ||||||||||||||||
1 | 5.6 | 12.2 | 43.7 | 17.4 | 45.8 | 46.5 | 58.9 | 63.3 | 66.2 | |||||||
2 | 13.1 | 28.5 | 58.1 | 34.7 | 55.9 | 54.3 | 71.6 | 63.6 | 73.2 | |||||||
3 | 7.6 | 21.7 | 39.1 | 19.6 | 39.7 | 44.1 | 53.7 | 60.9 | 67.2 | |||||||
4 | 9.4 | 26.3 | 46.4 | 31.3 | 51.4 | 57.6 | 69.4 | 75.6 | 79.1 |
Primary IM refractory CML-BC or AML cells with FLT-3 with ITD or point mutation were treated with the indicated concentrations of LBH589 and/or 17-AAG for 48 hours and the percent of nonviable cells was determined by the trypan blue exclusion method. The values represent the mean of 2 experiments performed in duplicate.