Our results demonstrated that the pan PI3K isoform inhibitor ZSTK474, the p110α inhibitor BYL719 and the IPI145 dual p110γ/p110δ inhibitor exerted the most powerful effects in all the Ph+ B-ALL cell lines tested and their combined use with TKIs enhanced the treatment efficacy. The gene discussed is PIK3CA; the disease is acute lymphoblastic leukemia.