Article Figures & Data
Figures
- Figure 1.
Patient-derived xenograft (PDX) and acute myeloid leukemia (AML) co-clinical model development. A) Patient and PDX characteristics of CTG-2241, an AML sample that previously failed to engraft in juvenile NOD/Shi-scid-IL2rγnull (NOG) mice. B) Humerus bone stained for huCD33+ and H&E. C) Immunohistochemical confirmation for co-clinical sample engraftment. D) Time to engraftment for pharmacology studies using bone marrow samples. Each symbol represents a different study. Values are expressed as mean±SE (N=10). E) Extent of engraftment during the expansion phase for pharmacology studies. Values are expressed as mean±SE (N=10).
- Figure 2.
Patient-derived xenograft (PDX) results (blasts/μl) in blood, bone marrow, and spleen compartments: pharmacology models derived from subjects that received mivebresib (ABBV-075) and venetoclax (VEN) combination therapy. ABBV-744 is another BET inhibitor that was evaluated in vivo in comparison with mivebresib. Values are expressed as mean±SE (N=4-10). *Indicates mean differs significantly (p<0.05) from vehicle.
- Figure 3.
Efficacy of bromodomain and extra-terminal motif (BET) inhibitors in co-clinical models. A) Inhibition of blast counts in blood, bone marrow and spleen from pharmacology models derived from subjects that received monotherapy or venetoclax combination therapy. Illustrated results include mivebresib and ABBV-744 monotherapy groups and groups in combination with venetoclax (indicated by the “+VEN” suffix). *Indicates that the mean of blasts differs significantly from vehicle (p<0.05). B) Effect of therapeutic agents on time to endpoint in a co-clinical patient-derived xenograft model derived from a patient receiving monotherapy (model #13, days 0-28). Treatment, median survival, and statistical analysis vs. vehicle are given in the legend (*p<0.05; **p<0.01; ***p<0.005).
- Figure 4.
Comparison of patient-derived xenograft model results to patient response. A) Clinical, biological activity, defined as ≥50% decrease in blast count. B) Mutational profile.
