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

• 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
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• 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 / BCR-ABL1点突然変異解析 / BCR-ABL1遺伝子点突然変異 / チロシンキナーゼ阻害剤 / 腫瘍診断学 / 薬物評価と予測 / 薬効評価と予測

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.

Research Products

• [Journal Article] Expression of CD56 is an unfavorable prognostic factor for acute promyelocytic leukemia with higher initial white blood cell counts. (2014)
  • Author(s): Ono T, Takeshita A, Kishimoto Y, Kiyoi H, Okada M, Yamauchi T, Emi N, Horikawa K, Matsuda M, Shinagawa K, Monma F, Ohtake S, Nakaseko C, Takahashi M, Kimura Y, Iwanaga M, Asou N, Naoe T; Japan Adult Leukemia Study Group.
  • Journal Title: Cancer Sci Volume: 105 Issue: 1 Pages: 97-104
  • DOI: 10.1111/cas.12319
  • Peer Reviewed / Open Access
• [Journal Article] Long-term outcome and prognostic factors of elderly patients with acute promyelocytic leukemia (2012)
  • Author(s): Ono T, Takeshita A, Kishimoto Y, Kiyoi H, Okada M, Yamauchi T, Tsuzuki M, Horikawa K, Matsuda M, Shinagawa K, Monma F, Ohtake S, Nakaseko C, Takahashi M, Kimura Y, Iwanaga M, Asou N, Naoe T
  • Journal Title: Cancer Sci. Volume: 103 Issue: 11 Pages: 174-1978
  • DOI: 10.1111/j.1349-7006.2012.02390.x
  • Peer Reviewed
• [Presentation] Long-Term Outcome Of Acute Promyelocytic Leukemia (APL) With Lower Initial Leukocyte Counts By Using All-Trans Retinoic Acid (ATRA) Alone For Remission Induction Therapy: Japan Adult Leukemia Study Group (JALSG) APL97 Study (2013)
  • Author(s): Takaaki Ono
  • Organizer: 55th Annual Meeting of American Society of Hematology
  • Place of Presentation: New Orleans, LA, USA