Figure 6.
KPT-9274 combines synergistically with niraparib to effectively target NAMPT-deficient AML. (A) Dose-response matrix (top) and analysis of 3-dimensional (3D) graph of ZIP synergy scores (bottom) after KPT-9274 is combined with nirpaparib for 72 hours in NAMPT-deficient OCI-AML3 clonal cell line (n = 3) (B) Dose-response matrix (top) and analysis of 3D graph of ZIP synergy scores (bottom) after KPT-9274 is combined with niraparib for 72 hours in P53 null NAMPT-deficient OCI-AML3 clonal cell line (n = 3; synergy score less than –10, antagonistic interaction; more than –10 and <10, additive interaction; and >10, synergistic interaction). (C) Model; NAMPT haploinsufficiency is a collateral lethal therapeutic vulnerability in high-risk −7/del(7q) myeloid malignancies.

KPT-9274 combines synergistically with niraparib to effectively target NAMPT-deficient AML. (A) Dose-response matrix (top) and analysis of 3-dimensional (3D) graph of ZIP synergy scores (bottom) after KPT-9274 is combined with nirpaparib for 72 hours in NAMPT-deficient OCI-AML3 clonal cell line (n = 3) (B) Dose-response matrix (top) and analysis of 3D graph of ZIP synergy scores (bottom) after KPT-9274 is combined with niraparib for 72 hours in P53 null NAMPT-deficient OCI-AML3 clonal cell line (n = 3; synergy score less than –10, antagonistic interaction; more than –10 and <10, additive interaction; and >10, synergistic interaction). (C) Model; NAMPT haploinsufficiency is a collateral lethal therapeutic vulnerability in high-risk −7/del(7q) myeloid malignancies.

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