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  • drug
  • The drug that you are taking for your cancer, imatinib (GleevecTM), has recently been shown to have some new types of side effects. (clinicaltrials.gov)
  • bone
  • This pilot study will collect longitudinal data on bone metabolism for patients treated with imatinib. (clinicaltrials.gov)
  • The effect of imatinib on bone may be dose-related. (clinicaltrials.gov)
  • We will determine the incidence of bone abnormalities in this treated population, determine whether fasting serum phosphate can predict for changes in bone metabolism, determine whether there is change in bone density by measuring serial bone densitometry, determine whether oral phosphate replacement can restore phosphate balance, and determine whether there is a dose effect of imatinib on parameters of bone metabolism. (clinicaltrials.gov)
  • The patient has at least two tests for quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for bcr-abl (peripheral blood or bone marrow aspirate). (knowcancer.com)
  • Determine the cytogenic response rate, in terms of Ph-positive progenitor cells in the bone marrow, in patients treated with this drug. (knowcancer.com)
  • Mouse bone marrow cells transduced with retroviral vectors encoding either of two oncogenic Bcr-Abl isoforms (p210 Bcr-Abl and p185 Bcr-Abl ) induce B cell lympholeukemias when transplanted into lethally irradiated mice. (pnas.org)
  • When mouse bone marrow cells expressing Bcr-Abl are placed in short-term cultures selectively designed to support the outgrowth of pre-B cells, only those lacking one or two Arf alleles can initiate lympholeukemias when inoculated into immunocompetent, syngeneic recipient mice. (pnas.org)
  • Although CML and Ph + ALL are triggered by very similar BCR-ABL oncoproteins, durable responses of Ph + ALL patients to imatinib therapy are uncommon ( 11 ), and these patients, both pediatric and adult, receive other conventional combinational chemotherapy and/or bone marrow transplants to stem their disease. (pnas.org)
  • It is a form of leukemia characterized by the increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood. (wikipedia.org)
  • Blast crisis is diagnosed if any of the following are present in a patient with CML: >20% myeloblasts or lymphoblasts in the blood or bone marrow Large clusters of blasts in the bone marrow on biopsy Development of a chloroma (solid focus of leukemia outside the bone marrow) The only curative treatment for CML is a bone marrow transplant or an allogeneic stem cell transplant. (wikipedia.org)
  • Imatinib was found to inhibit the progression of CML in the majority of patients (65-75%) sufficiently to achieve regrowth of their normal bone marrow stem cell population (a cytogenetic response) with stable proportions of maturing white blood cells. (wikipedia.org)
  • CML is characterized by an excessive and unregulated production of white blood cells by the bone marrow due to a genetic abnormality that produces the BCR-ABL protein. (wikipedia.org)
  • Absent these causes, patients were diagnosed in the World Health Organization's classification as having either 1) Chronic eosinophilic leukemia, not otherwise specified, (CEL-NOS) if blood or bone marrow blast cells exceeded 2% or 5% of total nucleated cells, respectively, and other criteria were met or 2) idiopathic hypereosinophilic syndrome (HES) if there was evidence of eosinophil-induced tissue damage but no criteria indicating chronic eosinophilic leukemia. (wikipedia.org)
  • resistant
  • However, recent clinical data indicate that ≈5% of patients per year who are maintained on imatinib become resistant to treatment. (pnas.org)
  • Therefore, second-generation kinase inhibitors, such as dasatinib, that effectively block the activity of most mutant forms of BCR-ABL are now being used to treat imatinib-resistant CML ( 9 , 10 ). (pnas.org)
  • However, subsets of patients lose their response to treatment through the emergence of imatinib-resistant cells, and imatinib treatment is less durable for patients with late stage CML. (nih.gov)
  • Here we report that a DNA sequence-specific pyrrole-imidazole polyamide-chlorambucil conjugate, 1R-Chl, causes growth arrest of cells harboring both unmutated BCR-ABL and three imatinib resistant strains. (nih.gov)
  • The observed additive effects of 1R-Chl and imatinib indicate that a cocktail of 1R-Chl with imatinib could potentially increase the efficacy of imatinib treatment and prevent the emergence of imatinib-resistant CML cells. (nih.gov)
  • In that study 92% of patients (already resistant or unresponsive to imatinib) achieved normal white blood cell counts after five months of treatment. (wikipedia.org)
  • Some forms of CML, those that have the T315I mutation, are resistant to current therapies such as imatinib. (wikipedia.org)
  • In 2010 ARIAD announced result from a Phase I study of ponatinib in patients with resistant and refractory chronic myeloid leukemia (CML) and Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). (wikipedia.org)
  • Second generation BCR-ABL tyrosine-kinase inhibitors are also under development to inhibit BCR-ABL mutants resistant to imatinib. (wikipedia.org)
  • myeloid leukaemia
  • hTERT, the catalytic component of telomerase, is downregulated in the haematopoietic stem cells of patients with chronic myeloid leukaemia. (ox.ac.uk)
  • Telomere shortening is associated with disease progression in chronic myeloid leukaemia (CML). (ox.ac.uk)
  • Dasatinib, nilotinib and standard-dose imatinib for the first-line treatment of chronic myeloid leukaemia: systematic reviews and economic analyses," Health Technology Assessment , vol. 16, no. 42, pp. 1-277, 2012. (hindawi.com)
  • kinases
  • The activity of tyrosine kinases is typically regulated in an auto-inhibitory fashion, but the BCR-Abl fusion gene codes for a protein that is "always on" or continuously activated leading to unregulated cell division (i.e. cancer). (wikipedia.org)
  • Although the BCR region also expresses serine/threonine kinases, the tyrosine kinase function is very relevant for drug therapy. (wikipedia.org)
  • The main targets of dasatinib are BCR/Abl (the "Philadelphia chromosome"), Src, c-Kit, ephrin receptors, and several other tyrosine kinases. (wikipedia.org)
  • New forms of resistance can arise as: missense mutations within the Abl kinase domain, over-expression of Bcr-Abl, increased production of transmembrane plasma proteins, or the constitutive activation of downstream signaling molecules such as Src-family kinases. (wikipedia.org)
  • dasatinib
  • The purpose of this clinical research study is to compare the rate of complete cytogenetic response of dasatinib to imatinib therapy at 6 months after randomization in chronic phase CML patients. (clinicaltrials.gov)
  • Though pulmonary-related adverse effects are rare when compared with imatinib and dasatinib, there is a case report of acute respiratory failure from diffuse alveolar hemorrhage in a patient taking nilotinib. (wikipedia.org)
  • cytogenetic
  • Complete cytogenetic response is defined as complete disappearance of Philadelphia-positive in at least 20 metaphases examined. (clinicaltrials.gov)
  • Resistance was defined according to the ELN guidelines 3 and if any hematological, cytogenetic or molecular progression ( i.e. increasing BCR-ABL/ABL ratio ≥ 2 logs) of CML in a previously IM-responsive patient was observed. (haematologica.org)
  • inhibition
  • Inhibition of colony formation by 1R-Chl and imatinib was additive in unmutated BCR-ABL-expressing murine BM (Fig. 3A). (nih.gov)
  • IRIS, an international study that compared interferon/cytarabine combination and the first of these new drugs imatinib, with long-term follow up, demonstrated the clear superiority of tyrosine-kinase-targeted inhibition over existing treatments. (wikipedia.org)
  • proteins
  • Since ABL activates a number of cell cycle-controlling proteins and enzymes, the result of the BCR-Abl fusion is to speed up cell division. (wikipedia.org)
  • mutations
  • The onset of ABL point mutations is the most frequent identified mechanism responsible for resistance. (haematologica.org)
  • This drug resistance is most often due to selection for secondary mutations in the BCR-ABL oncoprotein, rather than to "downstream" mutations affecting the signaling pathways subverted by the BCR-ABL kinase ( 8 ). (pnas.org)