Combined treatment with tyrosine kinase inhibitor plus PAI-1 inhibitor prolongs survival of chronic myeloid leukemia-bearing mice. (A) Schema for experiments. (B) Representative flow cytometric profiles for the percentage of chronic myeloid leukemia (CML) cells in the bone marrow (BM) at the indicated time points. (C) Analysis of spleen taken from imatinib (IM)- and IM plus plasminogen activator inhibitor-1 (PAI-1) inhibitor-treated mice (n=6). (D) Kaplan Meier survival curves of CML-bearing mice treated with saline (n=10), PAI-1 inhibitors (TM5275, TM5509, and TM5614) alone (n=10), IM alone (n=10), and IM plus PAI-1 inhibitor (n=15). (E) Percentages of leukemic cells in the BM (n=6). (F) Kaplan Meier survival curves of PAI-1 wild-type (PAI-1 WT) or PAI-1-overexpression (PAI-1 OE) CML cell-bearing mice treated with saline (n=0), IM alone (n=10), or IM plus PAI-1 inhibitor (TM5614) (n=10). Data represent means ± standard deviation. Statistical significance was determined by a log-rank non-parametric test (D, F) or Mann-Whitney unpaired t-test (E). P<0.001, by a Kruskal-Wallis test. SSC: side scatter.