Transplantation and therapeutic targeting of the transcriptional activity of Myb. (A) Scheme of primary transplantation of MybVav tumor cells into immunocompromised nonobese diabetic/severely compromised immunodeficiency γ (NSG) mice. (B) Bioluminescence of a primary BM tumor sample from Mybvav mouse #2 that was transplanted in an NSG mouse. Bioluminescence was measured over time. (C) Flow cytometry analysis of myeloid (Gr-1+Cd11b+) and B cells (B220+CD19+) of a control NSG and NSGs that were transplanted primary Mybvav tumor cells. (D) Graphs showing the percentage of B cells or myeloid cells which were pregated for single live cells. (E) Luciferase assay on Mybvav transplants. (F) Violin plots showing CERES cell dependency scores for MYB from AML (n = 20), ALL (n = 10), and 772 other cancer cell lines which were taken from DepMap (https://depmap.org/portal/). CERES is a computational method that estimates gene dependency based on data from CRISPR-Cas9 screens. A CERES score of 0 indicates that MYB is not essential, while a lower score indicates a higher likelihood that MYB is essential in a given cell line. MYB, AML, and ALL cell lines had a significantly lower CERES score than other cell lines. ****P < .0001. (G) Graphs depicting the survival of myeloid, B-cell, and mixed MybVav hematopoietic malignancies, which were treated for 48 hours with increasing concentrations of either MYBMIM or TG3.