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BCR‐ABL1 kinase domain mutations: Methodology and clinical evaluation
Author(s) -
Alikian Mary,
Gerrard Gareth,
Subramanian Papagudi G.,
Mudge Katherine,
Foskett Pierre,
Khorashad Jamshid Sorouri,
Lim Ai Chiin,
Marin David,
Milojkovic Dragana,
Reid Alistair,
Rezvani Katy,
Goldman John,
Apperley Jane,
Foroni Letizia
Publication year - 2012
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.22272
Subject(s) - imatinib , myeloid leukemia , nilotinib , tyrosine kinase , medicine , acquired resistance , oncology , clone (java method) , dasatinib , abl , mutation , imatinib mesylate , cancer research , bioinformatics , biology , genetics , gene , cancer , receptor
The introduction of tyrosine kinase inhibitors (TKIs), starting with imatinib and followed by second and third generation TKIs, has significantly changed the clinical management of patients with chronic myeloid leukemia (CML). Despite their unprecedented clinical success, a proportion of patients fail to achieve complete cytogenetic remission by 12 months of treatment (primary resistance) while others experience progressive resistance after an initial response (secondary resistance). BCR‐ABL1 kinase domain (KD) mutations have been detected in a proportion of patients at the time of treatment failure, and therefore their identification and monitoring plays an important role in therapeutic decisions particularly when switching TKIs. When monitoring KD mutations in a clinical laboratory, the choice of method should take into account turnaround time, cost, sensitivity, specificity, and ability to accurately quantify the size of the mutant clone. In this article, we describe in a “manual” style the methods most widely used in our laboratory to monitor KD mutations in patients with CML including direct sequencing, D‐HPLC, and pyrosequencing. Advantages, disadvantages, interpretation of results, and their clinical applications are reviewed for each method. Am. J. Hematol., 2012. © 2011 Wiley Periodicals, Inc.