Data as imply S.E.M., n=6. and therapeutics index of paclitaxelin vivo. Further, the molecular mechanism pertaining to pac-induced cytotoxicity was analyzed by studying the involvement of different apoptotic pathway proteins by immunoblotting and quantitative PCR. Our study revealed simultaneous activation of JNK pathway leading to Bcr-Abl instability and the extrinsic apoptotic pathway after pac-MNPs treatment in two Bcr-Abl positive cell lines. In addition, the MRI data suggested the potential software of MNPs as imaging agent. Thus ourin vitroandin vivoresults Santacruzamate A strongly suggested the pac-MNPs as a future prospective theranostic tool for leukemia therapy. == Introduction == Amongst the different types of leukemias, chronic myelogenous leukemia (CML) is a clonal malignancy of the hematopoietic stem cells that arises from a 9; 22 chromosomal translocation which fuses the ABL proto-oncogene to the BCR gene encoding the fusion protein p210Bcr-Abl[1],[2]. The abnormal p210Bcr-Ablconstitutively activates tyrosine kinase activity and promotes leukemogenesis by inducing the phosphorylation of multiple downstream protein targets that mediate multiple growth promoting and anti-apoptotic signals. In mammalian cells, the unique MAPK users are the important signaling molecules in the control of cell proliferation and differentiation. These include extracellular signal-regulated kinases (ERKs), pAkt, stress-activated protein kinases (SAPKs)/c-Jun N-terminal kinases (JNKs) and the p38 MAPK. The ERK cascade is mainly activated by growth factors and is critical for proliferation and survival. Whereas, JNK and p38 are only weakly activated by growth factors, but are highly activated in response to a variety of stress signals including tumor necrosis factor and their activation is usually most frequently associated with induction of apoptosis[3]. In CML the Bcr-Abl gene enhances the cell proliferation by activating the ERK and pAkt pathways and by inhibiting the p38 and JNK pathways[1]. Chemotherapy is the main strategy to treat leukemia because unlike solid tumor, hematological malignant tumor cannot be cured by surgical treatment or radiation therapy. However, the major obstacle associated in chemotherapy is the resistance of leukemic cells to various chemotherapeutic brokers. This is because most of the anti-cancer drugs induce apoptosis by initiating the intrinsic mitochondrial, or cytochromec/Apaf-1/caspase-9 pathway. The apoptotic pathways in chronic myeloid leukemia are mainly blocked due to Bcr-Abl gene expression, p53 mutation and deficiency of Fas receptor and functional Apaf-1[4]. To reverse the resistance mechanism with simultaneously reducing the side effects during high dose chemotherapy, a encouraging approach is usually rendered through which the conventional chemotherapy could be combined with new strategies leading for the induction of apoptosis to leukemia cells. Paclitaxel is a potent antineoplastic agent against a wide variety of malignancies. It has been approved by the FDA for the treatment of breast cancer, ovarian cancer and non-small-cell lung cancer (NSCLC)[5]. At the cellular level, Paclitaxel mainly binds to the beta-tubulin subunits in microtubules and promotes polymerization of tubulin and disrupts microtubule dynamics, leading to a sustained mitotic arrest and ultimately to apoptotic cell death[6]. However, molecular pathways involved in the apoptotic process induced by this agent are still not known. Antimicrotubule brokers are known to induce phosphorylation and thus inactivation of the antiapoptotic users of the Bcl family such as Bcl-2[7],[8]. The efficacy of taxanes on human leukemic cell lines[9],[10]as well as their effectiveness in inducing apoptosisin vivo[11]and in new KRT13 antibody leukemia cells in primary cultures[12]have been investigated. Al Alami et al. have exhibited the dose-dependency and time-dependency of the anti-tumor effects of paclitaxel in leukemia[9]. Anti-leukemic activity of taxanes was Santacruzamate A analyzed in samples with chromosomal abnormalities associated with an unfavorable end result, such as the Bcr-Abl translocation (Philadelphia chromosome)[13]. The key problem associated with hematological malignancy is usually reduced sensitivity of tumor cells to cytotoxic drugs and the drug efflux pumps that gives rise to multi drug resistance (MDR). Nanomaterials are well known to have potential applications in disease diagnosis and Santacruzamate A therapeutics[14]. The application of the magnetic nanoparticles (MNPs) in the field of biomedical application such as magnetic drug delivery, magnetic resonance imaging, transfection, cell and tissue targeting, has pooled considerable attention due to their.