α6 deletion sensitizes murine leukemia cells to tyrosine kinase inhibition in vitro, and the combination of the in vivo deletion of α6 with tyrosine kinase inhibition eradicates leukemia cells. α6^fl/fl BCR-ABL1⁺ (p210) CreER^T2 and EmptyER^T2 cells were plated onto tissue culture plates (without further coating) and treated with tamoxifen (1.5 μM) and nilotinib (0.02 μM or 0.2 μM) for 5 days. (A) Deletion of α6 was determined by flow cytometry. (B) Cell viability was determined by annexin V detection using flow cytometry. The y-axis indicates the percentage of annexin V–positive cells. Mean ± standard deviation is shown. ***P < .001. (C) Bioluminescence imaging of mice injected with luciferase-labeled murine α6^fl/fl BCR-ABL1⁺ CreER^T2 and EmptyER^T2 ALL cells followed by treatment with tamoxifen to delete α6 with or without nilotinib on the indicated days after ALL cell injection. One in vivo experiment is shown. (D) Kaplan-Meier survival analysis for the MST determination in each group: EmptyER^T2 (n = 6), MST = 27 days; CreER^T2 (n = 5), MST = 54.5 days; EmptyER^T2 + nilotinib (n = 6), MST = 39.5 days; CreER^T2 + nilotinib (n = 5), MST = undefined because 4 of 5 mice remained alive until the end of follow-up. *P = .0001, log-rank test. (E) Detection of murine BCR-ABL1 (p210⁺) cells in spleen cells (SPCs) or BM by qRT-PCR. Error bars are from the 2 comparison groups (Empty ER^T2 + NTB vs CRE ER^T2 + NTB). (F) α6 deletion was confirmed by flow cytometry in BM cells from leukemic mice injected with α6^fl/fl BCR-ABL1⁺ CreER^T2 or EmptyER^T2 cells. Donor white blood cells (WBCs) were labeled with CD45.2⁺. (G) Flow cytometric analysis of WBCs from recipients of α6^fl/fl BCR-ABL1⁺ CreER^T2 or EmptyER^T2 cells treated with nilotinib. Donor WBCs were CD45.2⁺, and recipient WBCs were CD45.1⁺. (H) Genomic PCR of BCR-ABL1 was performed on cells isolated from the spleen and BM of mice treated with EmptyER^T2 + nilotinib (NTB) and CreER^T2 + NTB. Murine HPRT (mHPRT) was used as an internal PCR DNA control.