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Therapy of Chronic Myeloid Leukemia: Twilight of the Imatinib Era?

Chronic myeloid leukemia (CML) results from the clonal expansion of pluripotent hematopoietic stem cells containing the active BCR/ABL fusion gene produced by a reciprocal translocation of the ABL1 gene to the BCR gene. The BCR/ABL protein displays a constitutive tyrosine kinase activity and confers...

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Detalles Bibliográficos
Autores principales: Trela, Ewelina, Glowacki, Sylwester, Błasiak, Janusz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929284/
https://www.ncbi.nlm.nih.gov/pubmed/24634785
http://dx.doi.org/10.1155/2014/596483
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author Trela, Ewelina
Glowacki, Sylwester
Błasiak, Janusz
author_facet Trela, Ewelina
Glowacki, Sylwester
Błasiak, Janusz
author_sort Trela, Ewelina
collection PubMed
description Chronic myeloid leukemia (CML) results from the clonal expansion of pluripotent hematopoietic stem cells containing the active BCR/ABL fusion gene produced by a reciprocal translocation of the ABL1 gene to the BCR gene. The BCR/ABL protein displays a constitutive tyrosine kinase activity and confers on leukemic cells growth and proliferation advantage and resistance to apoptosis. Introduction of imatinib (IM) and other tyrosine kinase inhibitors (TKIs) has radically improved the outcome of patients with CML and some other diseases with BCR/ABL expression. However, a fraction of CML patients presents with resistance to this drug. Regardless of clinical profits of IM, there are several drawbacks associated with its use, including lack of eradication of the malignant clone and increasing relapse rate resulting from long-term therapy, resistance, and intolerance. Second and third generations of TKIs have been developed to break IM resistance. Clinical studies revealed that the introduction of second-generation TKIs has improved the overall survival of CML patients; however, some with specific mutations such as T315I remain resistant. Second-generation TKIs may completely replace imatinib in perspective CML therapy, and addition of third-generation inhibitors may overcome resistance induced by every form of point mutations.
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spelling pubmed-39292842014-03-16 Therapy of Chronic Myeloid Leukemia: Twilight of the Imatinib Era? Trela, Ewelina Glowacki, Sylwester Błasiak, Janusz ISRN Oncol Review Article Chronic myeloid leukemia (CML) results from the clonal expansion of pluripotent hematopoietic stem cells containing the active BCR/ABL fusion gene produced by a reciprocal translocation of the ABL1 gene to the BCR gene. The BCR/ABL protein displays a constitutive tyrosine kinase activity and confers on leukemic cells growth and proliferation advantage and resistance to apoptosis. Introduction of imatinib (IM) and other tyrosine kinase inhibitors (TKIs) has radically improved the outcome of patients with CML and some other diseases with BCR/ABL expression. However, a fraction of CML patients presents with resistance to this drug. Regardless of clinical profits of IM, there are several drawbacks associated with its use, including lack of eradication of the malignant clone and increasing relapse rate resulting from long-term therapy, resistance, and intolerance. Second and third generations of TKIs have been developed to break IM resistance. Clinical studies revealed that the introduction of second-generation TKIs has improved the overall survival of CML patients; however, some with specific mutations such as T315I remain resistant. Second-generation TKIs may completely replace imatinib in perspective CML therapy, and addition of third-generation inhibitors may overcome resistance induced by every form of point mutations. Hindawi Publishing Corporation 2014-01-30 /pmc/articles/PMC3929284/ /pubmed/24634785 http://dx.doi.org/10.1155/2014/596483 Text en Copyright © 2014 Ewelina Trela et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Trela, Ewelina
Glowacki, Sylwester
Błasiak, Janusz
Therapy of Chronic Myeloid Leukemia: Twilight of the Imatinib Era?
title Therapy of Chronic Myeloid Leukemia: Twilight of the Imatinib Era?
title_full Therapy of Chronic Myeloid Leukemia: Twilight of the Imatinib Era?
title_fullStr Therapy of Chronic Myeloid Leukemia: Twilight of the Imatinib Era?
title_full_unstemmed Therapy of Chronic Myeloid Leukemia: Twilight of the Imatinib Era?
title_short Therapy of Chronic Myeloid Leukemia: Twilight of the Imatinib Era?
title_sort therapy of chronic myeloid leukemia: twilight of the imatinib era?
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929284/
https://www.ncbi.nlm.nih.gov/pubmed/24634785
http://dx.doi.org/10.1155/2014/596483
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