Detection of ABL1 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.

INTRODUCTION: ABL1 kinase mutations represent a major mechanism of imatinib resistance in Philadelphia-positive (Ph+) patients. There is a paucity of data on ABL1 kinase mutations in Ph+ patients in Korea.

METHODS: We used restriction fragment mass polymorphism (RFMP) analysis to detect ABL1 kinase mutations in blood or bone marrow specimens from 80 Ph+ patients.

RESULTS: Fifty-seven patients met the criteria for inadequate molecular response (IMR). ABL1 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-ABL1 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 ABL1 kinase mutations with high frequencies.