Figure 5.

Combined TKI and venetoclax treatment inhibits Ph-like ALL proliferation in vivo. A–D, CRLF2-rearranged (n = 4) and (E) ABL1-rearranged (n = 1) Ph-like ALL PDX models were treated with vehicle or inhibitors (5 mice/cohort) as delineated above and followed by flow cytometric quantification of human CD10⁺/CD19⁺ ALL in murine peripheral blood (left) and in end-study spleens (middle and right). F, The luciferase-expressing ABL1-rearranged TVA-1 PDX model was followed by bioluminescent imaging [flux measured in photons per second (p/s) with scales as designated] with terminal splenic leukemia burden quantified by flow cytometry as in the other five models. TKI and venetoclax cotreatment significantly inhibited leukemia proliferation in vivo in most PDX models versus inhibitor monotherapy. Error bars represent ± SD. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001 using 2-way ANOVA for peripheral blood analyses over time and one-way ANOVA for end-study spleen analyses. ns, not significant.