• Miaomiao Zhao, Xiya Gui, Qiuling Wu, Linghui Xia, and Yadan Wang.
• Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan.
• Medicine (Baltimore). 2021 May 7; 100 (18): e25579e25579.

RationaleUntil recently, the survival rate in patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) was approximately 30%. Tyrosine kinase inhibitors (TKIs), which are a new class of drugs that target BCR-ABL fusion protein, have shown to be effective in treating Ph+ ALL in adults. However, the resistance mechanisms that promote the disease recurrence have altered the initial success of these revolutionary agents.Patient ConcernsA 71-year-old Chinese female patient who suffered from severe shoulder and back pain for 1 week.DiagnosisThe patient was diagnosed with Ph+ ALL (B-cell) because of the following items. Complete blood count showed extremely abnormal white blood cell count (26.26×109/l), hemoglobin concentration (65 g/l) and platelet count (14×109/l). And because that Bone marrow aspirate showed 72.5% lymphoblasts and 59.30% lymphoblasts were confirmed by flow cytometry (FCM). At mean time, Real-time fluorescent quantitative PCR analysis confirmed that the P190 BCR/ABL fusion gene expression was 5.9%. Karyotype analysis indicated the following: 45, XX, -7, t (922) (q34; q11) [cp3].InterventionsThe patient was treated with chemotherapy and different TKIs including imatinib, dasatinib, ponatinib, and bosutinib.OutcomesThe patient achieved complete remissions with different TKIs after diagnose but relapsed afterward and died of infection.LessonsMultidrug-resistant mutations within the BCR-ABL1 kinase domain are an emerging clinical problem for patients receiving sequential TKIs therapy. Acquisition of E255K/V-inclusive mutations is usually associated with ponatinib resistance, thus it is necessary to screen out new real pan-inhibitor compounds for all BCR/ABL mutations and figure out the potential efficacy of asciminib-based drug combinations in the future.Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.

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