Sonu Rebecca J, Jonas Brian A, Dwyre Denis M, Gregg Jeffrey P, Rashidi Hooman H
Department of Pathology and Laboratory Medicine, University of California Davis Medical Center, Sacramento, CA 95817, USA.
Department of Internal Medicine, Division of Hematology and Oncology, University of California Davis Medical Center, Sacramento, CA 95817, USA.
Case Rep Hematol. 2015;2015:458052. doi: 10.1155/2015/458052. Epub 2015 Apr 8.
Patients with BCR-ABL1 positive hematologic malignancies and Philadelphia-like B-lymphoblastic leukemia (B-ALL) are potential candidates for targeted therapy with tyrosine kinase inhibitors (TKI). Before TKIs, patients with B-ALL had a much worse prognosis and current treatments with targeted TKI therapy have improved outcomes. Thus, the detection of BCR-ABL1 is crucial and a false negative BCR-ABL1 result may adversely affect patient care. We report a case of a 76-year-old male with a new diagnosis of B-ALL who was initially found to be BCR-ABL1 negative by quantitative polymerase chain reaction (PCR). A concurrent qualitative PCR was performed which detected a positive BCR-ABL1 result that was confirmed by a next generation sequencing (NGS) based assay and identified as the rare fusion variant e1a3 of p190(BCR-ABL). Based on this result, the patient was placed on dasatinib as a targeted therapy. In the era of molecular diagnostic medicine and targeted therapy, it is essential to have an understanding of the limitations of molecular assays and to follow a comprehensive diagnostic approach in order to detect common abnormalities and rare variants. Incorporating NGS methods in an algorithmic manner into the standard diagnostic PCR-based approach for BCR-ABL1 will aid in minimizing false negative results.
BCR-ABL1阳性血液系统恶性肿瘤患者和费城样B淋巴细胞白血病（B-ALL）患者是酪氨酸激酶抑制剂（TKI）靶向治疗的潜在候选者。在TKI出现之前，B-ALL患者的预后要差得多，而目前的靶向TKI治疗改善了治疗结果。因此，BCR-ABL1的检测至关重要，BCR-ABL1结果假阴性可能会对患者护理产生不利影响。我们报告了一例76岁新诊断为B-ALL的男性患者，其最初通过定量聚合酶链反应（PCR）检测为BCR-ABL1阴性。同时进行的定性PCR检测到BCR-ABL1阳性结果，该结果通过基于下一代测序（NGS）的检测得到证实，并被鉴定为罕见的p190（BCR-ABL）融合变体e1a3。基于这一结果，该患者接受达沙替尼作为靶向治疗。在分子诊断医学和靶向治疗时代，了解分子检测的局限性并采用全面的诊断方法以检测常见异常和罕见变体至关重要。以算法方式将NGS方法纳入基于PCR的BCR-ABL1标准诊断方法将有助于最大限度地减少假阴性结果。
