Francois Xavier Mahon

..The possible role of MDR overexpression in clinical resistance to imatinib remains to be defined. We therefore confirm that imatinib should be added to the extensive list of drugs that can be affected by the MDR phenomenon...

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..We aimed to assess whether imatinib can be discontinued without occurrence of molecular relapse in patients in complete molecular remission (CMR) while on imatinib...

..These new specific drugs and their effects on the chronic myelogenous leukemia must be taken into account to explain the physiopathology of the disease...

..Thus BCR-ABL inhibition restores the cytokine dependence but is not sufficient to induce apoptosis when other signaling pathways are activated...

..Interestingly, a lethal effect was also observed in the more immature CD34(+)CD38(-) TKI-insensitive population. Combination therapy might by an interesting strategy for the treatment of CML patients...

..It can be used to evaluate patient adherence to daily oral therapy, drug-drug interactions, or pharmacokinetic/pharmacodynamic relationships...

..6%; P = .021). Hence, we demonstrated the usefulness of these single nucleotide polymorphisms in the identification of CML who may or may not respond optimally to imatinib...

..Such mechanisms of resistance are close to those observed in imatinib-resistant cell lines and emphasize the critical role of Lyn in nilotinib resistance...

..We conclude that an oncogenic signaling mediated by Lyn and Syk can bypass the need of Bcr-Abl in CML cells. Thus, targeting these kinases may be of therapeutic value to override imatinib or nilotinib resistance in CML...

..In contrast, the induced decreased expression of Hsc70 was accompanied by a greater overexpression of Hsp70. This proteomic study therefore suggests opposing roles of Hsp70 and Hsc70 in imatinib resistance...

..However, only a minority of patients treated with imatinib have a complete molecular remission...

..STI571 is an original therapeutic approach which may be used as a model for the development of other drugs in cancer...

..These results show that MPA is an interesting tool to overcome resistance in vitro and in vivo mainly in the evolved phase of the disease...

..It allows evaluation of patient compliance, drug-drug interactions, and further investigations of pharmacokinetic/pharmacodynamic relationships...

..Triptolide has shown antitumor activity in a broad range of solid tumors and on leukemic cells in vitro...

..This stimulation is essential to explain their modulatory effect on the generation of clonogenic cells in cocultures EC/hematopoietic progenitors. Leukemia (2000) 14, 153-162...

..Therefore, monitoring of imatinib plasma levels could be very useful for the management of patients with CML or should at least be checked in the case of treatment failure or suboptimal response...

..MCR was defined as a reduction of Philadelphia chromosome-positive bone marrow cells to <or= 35%. The New CML score discriminated three risk groups with significantly different survival probabilities...

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..30%) for the cell lines and 13.6% (range 8.2-24.2%) for CD34+ HPC. These results indicate that liposome-mediated transfection of HC is significantly increased when cells are grown in adherence to stroma or fibroblast monolayers...

..The local expression of neurotrophin genes suggests a wide range of paracrine and/or autocrine mode of action through their corresponding receptors within the bone marrow...

..Therefore ex vivo expansion of putatively normal hematopoietic progenitor cells from cytapheresis is feasible in CML...

..32; P = .01). A landmark analysis performed at day 185 after CR1 confirmed a lower CIR after allo. RIC-allo reduces the risk of relapse, suggesting a potent graft-versus-leukemia (GVL) effect in these patients at a high risk of relapse...

..The anti-viral agent ribavirin and the immunosuppressant mycophenolic acid (MPA) are potent inhibitors of IMPDH. We recently showed that IMPDH inhibition led to a necrotic signal requiring the activation of Cdc42...

..We conclude that the c-KIT pathway may substitute for BCR-ABL tyrosine kinase to activate survival signals, and that c-KIT must be inhibited besides Bcr-Abl to allow apoptosis of CML cells...

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..Although protein expression did not consistently match mRNA levels, a role for the two cell cycle regulators in the IFN-alpha signaling pathway is suggested as well as a relation with the resistance to IFN-alpha or imatinib therapy...

..This study also illustrates the hypothesis that persistence of low numbers of Ph-positive cells does not necessarily imply hematologic relapse...

..Moreover, increased levels of PDGF and stimulatory autoantibodies to PDGFR have been identified in the serum of scleroderma patients...

..These experiments provide new insights into the pathogenesis of JAK2V617F MPD and demonstrate that a JAK2 inhibitor needs to target the HSC compartment for optimal disease control in classical MPD...

..As the 7q and 8q breakpoints were similar in both cases, the involvement of these critical regions in the pathogenesis and outcome of APL disease has to be determined...

..0001). (Blood. 2001;97:3568-3573)..

..Moreover, the overexpression of Hsp70 detected in imatinib-resistant CML patients supports this mechanism and identifies potentially a marker and a therapeutic target of CML evolution...