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Detection of ABL 1 kinase mutations in Philadelphia‐positive patients exhibiting an inadequate molecular response using restriction fragment mass polymorphism and its clinical significance: a single‐center experience in Korea
Author(s) -
Cho Y.U.,
Kim S.O.,
Chi H.S.,
Park S.J.,
Jang S.,
Park C.J.,
Seo E.J.,
Lee J.H.,
Lee J.H.,
Lee K.H.,
Im H.J.,
Seo J.J.,
Hong S. P.
Publication year - 2013
Publication title -
international journal of laboratory hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.705
H-Index - 55
eISSN - 1751-553X
pISSN - 1751-5521
DOI - 10.1111/ijlh.12091
Subject(s) - chronic myelogenous leukemia , abl , restriction fragment length polymorphism , imatinib , mutation , kinase , medicine , cancer research , leukemia , imatinib mesylate , microbiology and biotechnology , biology , genetics , gene , polymerase chain reaction , tyrosine kinase , myeloid leukemia , receptor
Summary Introduction ABL 1 kinase mutations represent a major mechanism of imatinib resistance in Philadelphia‐positive (Ph+) patients. There is a paucity of data on ABL 1 kinase mutations in Ph+ patients in Korea. Methods We used restriction fragment mass polymorphism ( RFMP ) analysis to detect ABL 1 kinase mutations in blood or bone marrow specimens from 80 Ph+ patients. Results Fifty‐seven patients met the criteria for inadequate molecular response ( IMR ). ABL 1 kinase mutations were found in 2.6% of patients with chronic‐phase chronic myelogenous leukemia ( CML ), 25.0% of accelerated‐phase CML , 66.7% of blast‐phase CML , and in 58.3% with Ph+ acute lymphoblastic leukemia. Twelve mutations were identified: 7 T315I, 2 E255V, 1 E255K, 1 F359V, and 1 Y253H. The majority of mutation‐positive patients showed an unfavorable clinical course and often had an extra Ph or additional chromosomal abnormalities. Mutations were detected in two patients who had very low or absent BCR ‐ ABL 1 normalized ratios. Conclusion Mutation analysis should be performed in Ph+ patients exhibiting an IMR to imatinib. RFMP analysis is helpful for revising therapeutic strategies because it can sensitively detect clinically relevant ABL 1 kinase mutations with high frequencies.