Chronic myelogenous leukemia (CML) results from malignant transformation of a primitive hematopoietic cell by the BCR/ABL oncogene. The breakpoint cluster region/ABL (BCR/ABL) tyrosine kinase inhibitor imatinib mesylate (imatinib) is highly effective in inducing remissions in CML. However, the effects of imatinib on intracellular signaling in primary progenitor cells are not well described. We ...

Patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) have poor prognosis despite intensive therapeutic intervention. Recently, imatinib, a BCR-ABL tyrosine kinase inhibitor, has been proven to be an effective treatment for Ph(+) ALL, but nearly all patients rapidly acquire resistance. High-dose imatinib administration might overcome this resistance; however, s...

BACKGROUND For imatinib, a relationship between systemic exposure and clinical outcome has been suggested. Importantly, imatinib concentrations are not stable and decrease over time, for which several mechanisms have been suggested. In this study, we investigated if a decrease in alpha-1 acid glycoprotein (AGP) is the main cause of the lowering in imatinib exposure over time. METHODS We prosp...

Imatinib revolutionized the treatment of chronic myeloid leukemia (CML) with the expression of the BCR-ABL1 tyrosine kinase, but imatinib resistance is an emerging problem. Imatinib can hinder the inhibitory effects of BCR-ABL1 on mitochondrial apoptotic pathway, so mitochondrial mutagenesis can be important for its action. To explore the mechanisms of imatinib resistance we created a mouse-der...

Imatinib mesylate (Gleevec, STI571), a selective inhibitor of a restricted number of tyrosine kinases, has been effectively used for the treatment of Philadelphia chromosome-positive leukemias and gastrointestinal stromal tumors. Imatinib may also directly influence immune cells. Suppressive as well as stimulating effects of this drug on CD4(+) and CD8(+) T lymphocytes or dendritic cells have b...

Background Imatinib mesylate, a small-molecular analog of adenosine triphosphate (ATP) that potently inhibits tyrosine kinase activities of Bcr–Abl, PDGFR-β, PDGFR-α, c-Fms, Arg and c-kit, is one of the novel molecularly targeted drugs being introduced into cancer therapy. We tested the effect of imatinib on the ovarian histological structure and the concentration of estrogen and progesterone, ...

Imatinib mesylate (signal transduction inhibitor 571, Gleevec) is a potent and selective tyrosine kinase inhibitor, which was shown to effectively inhibit platelet-derived growth factor–induced glioblastoma cell growth preclinically. However, in patients, a limited penetration of imatinib into the brain has been reported. Imatinib is transported in vitro and in vivo by P-glycoprotein (P-gp; ABC...

Treatment with imatinib is very effective in Bcr-Abl positive leukemia. However, development of resistance to this drug is a common phenomenon in late stage disease. The Bcr-Abl protein localizes to the cytoplasm in transformed cells but can enter the nucleus upon treatment with imatinib. Using leptomycin B, a nuclear export blocker, it has been shown that reactivated nuclear Bcr-Abl kinase act...

While imatinib is highly effective therapy, with improving prospects over time for sustained remission and potential to severely limit or eliminate disease progression and transformation, a minority of patients either fail or respond suboptimally to imatinib; as well, disease eradication may not be possible with imatinib. Distinct patterns of resistance have evolved with the use of imatinib, an...

It was recently recognized that some chronic myeloid leukemia patients with a complete molecular response could sustain that response after discontinuation of imatinib. To characterize the clinical outcomes and profiles of chronic phase chronic myeloid leukemia patients who could discontinue imatinib, we conducted a nationwide survey in Japan. Among 3,242 imatinib-treated chronic myeloid leukem...