Table 3. Ex vivo 5-Azacytidine EC50 fold-shift enhancement by ABT-737.
| Primary sample type | Maximal 5-Aza EC50 fold-shift; (ABT-737 dose) | Cytogenetics, mutations |
|---|---|---|
| De novo AML | 3.3 (1.3 μM) | Inv 16, FLT3 neg., NPM1 neg. |
| MDS → AML_1 | 2.7 (630 nM) | Restricted patient info. |
| MDS → AML_2 | −6.8 (2.5 μM) | +8 (1 of 20), FISH normal, FLT3 neg., NPM1 pos. |
| MDS → AML_3 | 1.1 (80 nM) | −7 (20 of 20, 90% by FISH), NPM1 neg. |
| PMF → AML | 2.1 (630 nM) | 46XY, JAK2 neg. |
| PV → MDS/MPN | 2.0 (1.3 μM) | 46XY, JAK2V617F pos. |
| RCMD MDS | 1.1 (160 nM) | Del 20 (8 of 20, 41% by FISH), JAK2 neg. |
| Low-grade MDS | 1.5 (1.3 μM) | 46XX, MDS FISH neg. |
| ET | 2.3 (1.3 μM) | 46XY, JAK2 neg., MPL neg. |
| PV_1 | 1.4 (310 nM) | 46XY, JAK2 pos. |
| PV_2 | 1.8 (1.3 μM) | JAK2 pos. |
Ex vivo 5-Azacytidine fold-shift enhancement by ABT-737. 5-Aza enhancement as determined by maximal 5-Aza EC50 shifts for the same 11 primary specimens shown in Figure 5 are shown with the dose of ABT-737 at which maximal EC50 enhancement occurred (shown in brackets), aside clinical cytogenetics and mutations. Although only doses corresponding to maximal enhancement are shown, significant enhancement often occurred at lower doses of ABT-737. Similarly, greater synergy by CI was frequently observed with increasing doses of 5-Aza beyond the EC50 dose. For example, see the MDS-to-AML_2 sample in Table 3 in comparison with this same sample in Figure 4, noting the antagonistic CI values near the lower, 2.5 μM 5-Aza EC50 dose (points 1–4), yet strong synergistic CI and FE at the higher 7.4 μM concentration of 5-Aza (points 5–8). ‘−' denotes antagonistic fold-shift.