The　clinical　outcome　of　chronic　myeloid　leukemia　(CML)　patients　has　been　changed　dramatically　due　to　the　development　of　imatinib　(IM).　However,　the　emergence　of　IM　resistance,　commonly　associated　with　point　mutations　within　the　BCR-ABL　kinase　domain,　remains　a　major　clinical　problem.　Here,　we　investigated　the　effects　of　E35,　a　novel　derivative　of　emodin,　on　the　IM-resistant　32Dp210-T315I　cells.　Cell　proliferation　was　measured　by　3-(4,5-dimethylthiazol-2-yl)-2,5　diphenyltetrazolium　bromide　and　colony　formation　assay.　Induction　of　apoptosis　was　confirmed　by　DNA　fragmentation　assay　and　annexin　V/PI　staining　assay.　Real-time　quantitative　PCR　was　used　to　access　the　BCR-ABL　gene　expression.　Changes　of　related　signaling　molecules　were　detected　through　Western　blot.　E35　was　found　to　potently　inhibit　proliferation　of　32Dp210-T315I　cells　with　an　average　IC50　of　2.4　A　mu　M　at　48　h.　Colony　formation　was　almost　fully　suppressed　in　1.0　mu　M　E35　group.　DNA　fragmentation　and　annexin　V/PI　staining　assay　exhibited　the　typical　DNA　fragmentation　and　the　increased　proportion　of　early　apoptotic　cells,　respectively.　The　induction　of　apoptosis　was　associated　with　increase　of　Bax　to　Bcl-2　expression　ratio　and　activation　of　caspase　cascades　involving　decrease　of　pro-caspase　9　and　pro-caspase　3　and　increase　of　PARP　cleavage.　The　protein　expression　of　P210(BCR-ABL)　and　p-P210(BCR-ABL)　was　down-regulated　in　the　presence　of　E35,　although　the　mRNA　levels　remained　almost　unchanged.　Moreover,　the　activation　of　the　P210(BCR-ABL)　downstream　signaling　pathways　including　CrkL,　Akt/mTOR　and　MEK/ERK　was　fully　suppressed　by　E35.　Our　study　indicated　that　E35　might　be　a　potential　antileukemia　agent　against　IM　resistance　in　CML.