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https://hdl.handle.net/2440/9306
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Type: | Journal article |
Title: | High frequency of point mutations clustered within the adenosine triphosphate-binding region of BCR/ABL in patients with chronic myeloid leukemia or Ph-positive acute lymphoblastic leukemia who develop imatinib (STI571) resistance |
Author: | Branford, S. Rudzki, Z. Walsh, S. Grigg, A. Arthur, C. Taylor, K. Herrmann, R. Lynch, K. Hughes, T. |
Citation: | Blood, 2002; 99(9):3472-3475 |
Publisher: | Amer Soc Hematology |
Issue Date: | 2002 |
ISSN: | 0006-4971 1528-0020 |
Abstract: | Point mutations were found in the adenosine triphosphate (ATP) binding region of BCR/ABL in 12 of 18 patients with chronic myeloid leukemia (CML) or Ph-positive acute lymphoblastic leukemia (Ph+ ALL) and imatinib resistance (defined as loss of established hematologic response), but they were found in only 1 of 10 patients with CML with imatinib refractoriness (failure to achieve cytogenetic response). In 10 of 10 patients for whom samples were available, the mutation was not detected before the initiation of imatinib therapy. Three mutations (T315I, Y253H, and F317L present in 3, 1, and 1 patients, respectively) have a predicted role in abrogating imatinib binding to BCR/ABL, whereas 3 other mutations (E255K, G250E, and M351T, present in 4, 2, and 2 patients, respectively) do not. Thus we confirm a high frequency of mutations clustered within the ATP-binding region of BCR/ABL in resistant patients. Screening may allow intervention before relapse by identifying emerging mutations with defined impacts on imatinib binding. Certain mutations may respond to higher doses of imatinib, whereas other mutations may mandate switching to another therapeutic strategy. |
Keywords: | Humans Benzamides Piperazines Pyrimidines Fusion Proteins, bcr-abl Adenosine Triphosphate DNA Mutational Analysis Binding Sites Drug Resistance, Neoplasm Gene Frequency Point Mutation Adult Aged Middle Aged Female Male Leukemia, Myelogenous, Chronic, BCR-ABL Positive Precursor Cell Lymphoblastic Leukemia-Lymphoma Imatinib Mesylate |
Description: | © 2002 by The American Society of Hematology. |
DOI: | 10.1182/blood.V99.9.3472 |
Published version: | http://bloodjournal.hematologylibrary.org/cgi/content/abstract/99/9/3472 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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