BCR-ABL1 mutations in patients with imatinib-resistant chronic myelogenous leukemia

2014 Fiscal Year Final Research Report

• Project/Area Number: 24501340
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor diagnosis
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: ONO TAKAAKI 浜松医科大学, 医学部附属病院, 助教 (40402276)
• Co-Investigator(Kenkyū-buntansha): OHNISHI Kazunori 浜松医科大学, 医学部附属病院, 教授 (80252170)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 慢性骨髄性白血病 / BCR-ABL1点突然変異 / PCR-インベーダー法 / イマチニブ

Outline of Final Research Achievements

The association between BCR-ABL1 kinase domain mutation and therapeutic response was evaluated in patients with chronic myelogenous leukemia（CML) using both PCR-Invader assay and direct sequencing to establish standard method for screening of mutations. BCR-ABL1 KD mutations were detected in 1 patient of 19 newly diagnosed CML and 4 of 6 tyrosine kinase inhibitor (TKI) resistant CML.Among detected mutations,exon 8/9 35-bp insertion (BCR-ABL135INS mutation) was observed in 3 patients with newly diagnosed CML (n=1) or TKI resistant CML (n=2). Our result showed that CML with BCR-ABL135INS mutation had resistance for imatinib, while this mutation had favorable response to nilotinib. PCR-Invader assay is useful for screening of mutations, although we should be careful for the undetectability of BCR-ABL135INS mutation by using this assay.

Free Research Field

医歯薬学