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Use and limitations of imatinib mesylate (Glivec), a selective inhibitor of the tyrosine kinase Abl transcript in the treatment of chronic myeloid leukaemia

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Use and limitations of imatinib mesylate (Glivec), a selective inhibitor of the tyrosine kinase Abl transcript in the treatment of chronic myeloid leukaemia. / Knight, Gavin; McLellan, D.

In: British Journal of Biomedical Science, Vol. 61, No. 2, 2004, p. 103-111.

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@article{a221d080f4a64137827ab3f55933f410,
title = "Use and limitations of imatinib mesylate (Glivec), a selective inhibitor of the tyrosine kinase Abl transcript in the treatment of chronic myeloid leukaemia",
abstract = "Chronic myeloid leukaemia is associated with a specific translocation between chromosomes 9 and 22 that results in the formation of a chimaeric gene. This gene, when transcribed, produces the BCR-Abl oncoprotein which hastyrosine kinase activity and the ability to prevent apoptosis, but has no effect on cellular proliferation. Imatinib mesylate, an inhibitor of the BCR-Abl transcript modelled on the ATP binding pocket of the Abl oncoprotein, prevents phosphorylation of effector molecules and induces apoptosis. Imatinib has limited effectiveness when BCR-Abl cells are in the quiescent cell-cycle state of G0. A life-long regimen of imatinib should reduce the risk of relapse from cells leaving Go. Up-regulation of BCR-Abl expression, ATP binding pocket mutations, up-regulation of MDR1 and over-expression of Pgp are all thought to limit the effectiveness of imatinib. Advanced BCR-Abl positivity is associated with complex mutations, which are thought to have a cumulative effect on the BCR-Abl oncoprotein in disrupting normal signal transduction, making these cells refractory to monotherapy alone. Combination therapy is thought to overcome this. Research studies have identified imatinib as a potential treatment option for a diverse range of malignancies associated with BCR-Abl, platelet-derived growth factor receptor (PDGFr) and c-Kit pathways. This may extend the application of this special therapy in the future.",
author = "Gavin Knight and D. McLellan",
year = "2004",
language = "English",
volume = "61",
pages = "103--111",
journal = "British Journal of Biomedical Science",
issn = "0967-4845",
publisher = "Step Publishing Ltd.",
number = "2",

}

RIS

TY - JOUR

T1 - Use and limitations of imatinib mesylate (Glivec), a selective inhibitor of the tyrosine kinase Abl transcript in the treatment of chronic myeloid leukaemia

AU - Knight, Gavin

AU - McLellan, D.

PY - 2004

Y1 - 2004

N2 - Chronic myeloid leukaemia is associated with a specific translocation between chromosomes 9 and 22 that results in the formation of a chimaeric gene. This gene, when transcribed, produces the BCR-Abl oncoprotein which hastyrosine kinase activity and the ability to prevent apoptosis, but has no effect on cellular proliferation. Imatinib mesylate, an inhibitor of the BCR-Abl transcript modelled on the ATP binding pocket of the Abl oncoprotein, prevents phosphorylation of effector molecules and induces apoptosis. Imatinib has limited effectiveness when BCR-Abl cells are in the quiescent cell-cycle state of G0. A life-long regimen of imatinib should reduce the risk of relapse from cells leaving Go. Up-regulation of BCR-Abl expression, ATP binding pocket mutations, up-regulation of MDR1 and over-expression of Pgp are all thought to limit the effectiveness of imatinib. Advanced BCR-Abl positivity is associated with complex mutations, which are thought to have a cumulative effect on the BCR-Abl oncoprotein in disrupting normal signal transduction, making these cells refractory to monotherapy alone. Combination therapy is thought to overcome this. Research studies have identified imatinib as a potential treatment option for a diverse range of malignancies associated with BCR-Abl, platelet-derived growth factor receptor (PDGFr) and c-Kit pathways. This may extend the application of this special therapy in the future.

AB - Chronic myeloid leukaemia is associated with a specific translocation between chromosomes 9 and 22 that results in the formation of a chimaeric gene. This gene, when transcribed, produces the BCR-Abl oncoprotein which hastyrosine kinase activity and the ability to prevent apoptosis, but has no effect on cellular proliferation. Imatinib mesylate, an inhibitor of the BCR-Abl transcript modelled on the ATP binding pocket of the Abl oncoprotein, prevents phosphorylation of effector molecules and induces apoptosis. Imatinib has limited effectiveness when BCR-Abl cells are in the quiescent cell-cycle state of G0. A life-long regimen of imatinib should reduce the risk of relapse from cells leaving Go. Up-regulation of BCR-Abl expression, ATP binding pocket mutations, up-regulation of MDR1 and over-expression of Pgp are all thought to limit the effectiveness of imatinib. Advanced BCR-Abl positivity is associated with complex mutations, which are thought to have a cumulative effect on the BCR-Abl oncoprotein in disrupting normal signal transduction, making these cells refractory to monotherapy alone. Combination therapy is thought to overcome this. Research studies have identified imatinib as a potential treatment option for a diverse range of malignancies associated with BCR-Abl, platelet-derived growth factor receptor (PDGFr) and c-Kit pathways. This may extend the application of this special therapy in the future.

M3 - Article

VL - 61

SP - 103

EP - 111

JO - British Journal of Biomedical Science

JF - British Journal of Biomedical Science

SN - 0967-4845

IS - 2

ER -

ID: 165870