alexa Chronic myeloid leukemia: clinical impact of BCR-ABL1 mutations and other lesions associated with disease progression.
Oncology

Oncology

Chemotherapy: Open Access

Author(s): Ernst T, Hochhaus A

Abstract Share this page

The introduction of the tyrosine kinase inhibitors (TKIs) imatinib, dasatinib, and nilotinib has dramatically improved the treatment of chronic myeloid leukemia (CML). However, a minority of CML patients in chronic phase (CP) and a substantial proportion of patients in advanced phase are either initially refractory to TKIs or eventually develop resistance. Rates of resistance and relapse directly correlate with disease progression. The most frequently identified mechanism of acquired TKI resistance is BCR-ABL1 kinase domain (KD) mutations that impair TKI binding by disrupting the drug contact sites or causing conformational changes that make the contact sites inaccessible. The underlying mechanisms of disease progression are heterogeneous and only poorly understood. So far the most frequent and best characterized include genomic instability, loss of tumor-suppressor functions, and differentiation arrest. Clinical data indicate that both development of a BCR-ABL1 KD mutation during TKI treatment and/or disease progression are associated with a poorer outcome. Thus, therapeutic strategies are needed for the treatment or prevention of resistance and disease progression. They include, for example, TKI dose escalation, treatment interruption to stop selection of resistant cells, and allogeneic stem cell transplantation in eligible patients, as well as the use of novel TKIs with activity against resistant mutations and/or inhibition of alternative pathways.

  • To read the full article Visit
  • Subscription
This article was published in Semin Oncol. and referenced in Chemotherapy: Open Access

Relevant Expert PPTs

Relevant Speaker PPTs

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords