Search results for " bcr-abl"
showing 10 items of 70 documents
Interleukin 3- receptor targeted exosomes inhibit in vitro and in vivo chronic myelogenous Leukemia cell growth
2017
Despite Imatinib (IM), a selective inhibitor of Bcr-Abl, having led to improved prognosis in Chronic Myeloid Leukemia (CML) patients, acquired resistance and long-term adverse effects is still being encountered. There is, therefore, urgent need to develop alternative strategies to overcome drug resistance. According to the molecules expressed on their surface, exosomes can target specific cells. Exosomes can also be loaded with a variety of molecules, thereby acting as a vehicle for the delivery of therapeutic agents. In this study, we engineered HEK293T cells to express the exosomal protein Lamp2b, fused to a fragment of Interleukin 3 (IL3). The IL3 receptor (IL3-R) is overexpressed in CML…
Identification of NM23-H2 as a tumour-associated antigen in chronic myeloid leukaemia.
2008
Therapeutic effects of haematopoietic stem cell transplantation are not limited to maximal chemoradiotherapy and subsequent bone marrow regeneration, but include specific as well as unspecific immune reactions known as graft-versus-leukaemia (GvL) effects. Specific immune reactions are likely to be particularly relevant to the long-term treatment of diseases, such as chronic myeloid leukaemia (CML), in which residual cells may remain quiescent and unresponsive to cytotoxic and molecular therapies for long periods of time. Specific GvL effects result from the expression on leukaemic cells of specific tumour-associated antigens (TAAs) in the context of HLA proteins. As human leukocyte antigen…
Current results on the use of imatinib mesylate in patients with relapsed philadelphia chromosome positive leukemia after allogeneic or syngeneic hem…
2003
Here, we describe a patient diagnosed with chronic myelogenous leukemia who relapsed after matched unrelated donor SCT. The patient was treated with imatinib mesylate and donor lymphocyte infusions, and achieved a complete molecular remission. Additionally, safety and efficacy of imatinib mesylate in a total of 134 patients from 8 centers who underwent allogeneic or syngeneic stem cell transplantation (SCT) and had a relapse of Philadelphia chromosome positive leukemia was reviewed. Data was compiled from abstracts accepted as oral or poster presentations at the ASH (American Society of Hematology) 2001 and EBMT (European Group for Blood and Marrow Transplantation) 2001 & 2002 meetings and …
Immunophenotypical comparison of Gaucher's and pseudo-Gaucher cells.
1996
An immunohistochemical study on bone marrow biopsies and spleens of patients with Gaucher's disease and chronic myeloid leukemia was performed to investigate the immunophenotype of Gaucher's cells and pseudo-Gaucher cells. A panel of antibodies was used which were reactive on paraffin-embedded tissues and directed against different hematopoietic lineage cells. Gaucher's cells and pseudo-Gaucher cells expressed a very similar immunophenotype and displayed an intense reaction for the monocytic antibodies tested, thus confirming their common origin and that they belong to the same system. The expression of HLA-DR antigens was much stronger in Gaucher's than in pseudo-Gaucher cells. This last f…
The prognosis for patients with chronic myeloid leukemia who have clonal cytogenetic abnormalities in philadelphia chromosome-negative cells.
2007
BACKGROUND. Clonal cytogenetic abnormalities (CCA) were detected in Philadelphia chromosome (Ph)-negative cells in some patients with chronic myeloid leukemia (CML) who attained a cytogenetic response to imatinib mesylate. In some patients, CCA/Ph-negative status was associated with myelodysplasia or acute myeloid leukemia. The objective of the current study was to determine the prognostic impact of CCA/Ph-negative cells. METHODS. The authors compared the pretherapeutic risk factors (Kruskall-Wallis test), exposure to cytotoxic drugs (chi-square test), and overall and progression-free survival (Kaplan-Meyer and logistic regression analysis, respectively) of 515 patients with mostly chronic-…
Synthesis and in vitro antileukemic activity of new 4-triazenopyrazole derivatives
2003
Several new 4-(3,3-dimethyltriazeno)-5-benzamidopyrazole derivatives were prepared by reacting 4-diazo-5-benzamidopyrazole derivatives with dimethylamine. The compounds were tested at 10 microM for their vitro antileukemic activity against K562 (Human chronic myelogenous leukemia) and Raji (human Burkitt limphoma ) cell lines. Dacarbazine and methotrexate were used for comparative purpose. The 3-methyl-4-(3,3-dimethyltriazeno)-5-(substituted benzamido)pyrazoles, bearing the pyrazole nucleus free at 1 position, resulted more active than the 1-(substituted phenyl)-3-methyl-4-(3,3-dimethyltriazeno)-5-benzamidopyrazoles. Dacarbazine at 10 microM showed no activity in the above tests. The observ…
The new HFA/ICOS risk assessment tool to identify patients with chronic myeloid leukaemia at high risk of cardiotoxicity
2022
AimsTyrosine kinase inhibitors (TKIs) used to treat chronic myeloid leukaemia (CML) can cause cardiovascular adverseevents. So far, the Systematic Coronary Risk Evaluation (SCORE) charts of the European Society of Cardiology (ESC) have beenused to identify cancer patients at increased cardiovascular risk. The primary aim of our study was to evaluate the usefulnessof the new cardiovascular risk assessment model proposed by the Cardio-Oncology Study Group of the Heart Failure Associ-ation (HFA) of the ESC in collaboration with the International Cardio-Oncology Society (ICOS) to stratify the cardiovascular riskin CML patients, compared with SCORE risk charts. The secondary aim was to establish…
BCR-ABL as a target for novel therapeutic interventions.
2002
The BCR-ABL oncogene is the result of a reciprocal translocation between the long arms of chromosome 9 and 22 t(9; 22). There is good experimental evidence demonstrating that BCR-ABL is the single causative abnormality in chronic myeloid leukaemia (CML), making it a unique model for the development of molecular targets. In addition to CML, BCR-ABL transcripts can be found in a minority of acute lymphoblastic leukaemias and very rarely in acute myeloid leukaemia (AML). Elucidating the molecular mechanisms and downstream pathways of BCR-ABL has led to the design of several novel therapeutic approaches. In this review, molecular targeting of BCR-ABL will be discussed based on the inhibition of…
Chronic myeloid leukemia-derived exosomes promote tumor growth through an autocrine mechanism.
2014
Background Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder in which leukemic cells display a reciprocal t(9:22) chromosomal translocation that results in the formation of the chimeric BCR-ABL oncoprotein, with a constitutive tyrosine kinase activity. Consequently, BCR-ABL causes increased proliferation, inhibition of apoptosis, and altered adhesion of leukemic blasts to the bone marrow (BM) microenvironment. It has been well documented that cancer cells can generate their own signals in order to sustain their growth and survival, and recent studies have revealed the role of cancer-derived exosomes in activating signal transduction pathways involved in cancer cell…
SWATH-MS based quantitative proteomics analysis reveals that curcumin alters the metabolic enzyme profile of CML cells by affecting the activity of m…
2018
Background Chronic myelogenous leukemia (CML) is a myeloproliferative disorder caused by expression of the chimeric BCR-ABL tyrosine kinase oncogene, resulting from the t(9;22) chromosomal translocation. Imatinib (gleevec, STI-571) is a selective inhibitor of BCR-ABL activity highly effective in the treatment of CML. However, even though almost all CML patients respond to treatment with imatinib or third generation inhibitors, these drugs are not curative and need to be taken indefinitely or until patients become resistant. Therefore, to get a definitive eradication of leukemic cells, it is necessary to find novel therapeutic combinations, for achieving greater efficacy and fewer side effec…