The role of E255K/V-inclusive mutations in a Philadelphia-positive acute lymphoblastic leukemia with mutation evolution during sequential TKIs therapies: A case report. Issue 18 (7th May 2021)

• Record Type: Journal Article
• Authors: Zhao, Miaomiao; Gui, Xiya; Wu, Qiuling; Xia, Linghui; Wang, Yadan
• Other Names: Saranathan. Maya section editor.
• Is Part Of: Medicine. Volume 100:Issue 18(2021)
• Publication Date: 2021-05-07
• Subjects: BCR-ABL1 mutation -- clonal evolution -- compound mutation -- E255K/V-inclusive mutation -- Philadelphia chromosome-positive acute lymphoblastic leukemia -- ponatinib; Medicine -- Periodicals; Medicine -- Periodicals; Médecine -- Périodiques; Geneeskunde; Medicine; Periodicals; Periodicals; 610.5
• DOI: 10.1097/MD.0000000000025579
• Languages: English
• ISSNs: 0025-7974

Abstract

Abstract: Rationale: Until 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 concerns: A 71-year-old Chinese female patient who suffered from severe shoulder and back pain for 1 week. Diagnosis: The patient was diagnosed with Ph+ ALL (B–cell) because of the following items. Complete blood count showed extremely abnormal white blood cell count (26.26×10 9 /l), hemoglobin concentration (65 g/l) and platelet count (14×10 9 /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]. Interventions: The patient was treated with chemotherapy and different TKIs including imatinib, dasatinib, ponatinib, and bosutinib. Outcomes: The patient achieved complete remissions with different TKIs after diagnose but relapsed afterward and died of infection. Lessons: Multidrug-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. Abstract : Supplemental Digital Content is available in the text