Sklarz Lisa-Madeleine, Wittke Christoph, Krohn Saskia, GROßE-Thie Christina, Junghanss Christian, Murua Escobar Hugo, Glaeser Hartmut
Department of Medicine, Clinic III - Hematology/Oncology/Palliative Medicine, Rostock University Medical Center, Rostock, Germany.
Department of Medicine, Clinic III - Hematology/Oncology/Palliative Medicine, Rostock University Medical Center, Rostock, Germany
Anticancer Res. 2018 Jul;38(7):3961-3966. doi: 10.21873/anticanres.12682.
Since the introduction of tyrosine kinase inhibitors (TKI), the prospects for patients with chronic myeloid leukemia (CML) have improved significantly. Herein we present the case of a patient with CML who experienced blast crisis and development of acute myeloid leukemia (AML) 10 years after presentation. The CML was characterized by the gene fusion of breakpoint cluster region BCR and tyrosine-protein kinase ABL1. During treatment different therapeutic protocols including imatinib, nilotinib, dasatinib and ponatinib were applied due to development of resistance or non-response. Fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) were used to describe cytogenetic and molecular aberrations elucidating the development into AML: A loss of chromosome 7, as well as an arising frequency of variants in the gene met proto-oncogene MET (p.T110I) and tyrosine-protein phosphatase non-receptor type 11 PTPN11 (p.Q510L) was observed. This report describes the comprehensive characterization of a clinical case showing multiple therapeutic resistances correlated with genetic aberrations.
自酪氨酸激酶抑制剂（TKI）问世以来，慢性髓性白血病（CML）患者的预后有了显著改善。在此，我们报告一例CML患者，其在确诊10年后发生了急变期并发展为急性髓性白血病（AML）。该CML的特征是断裂点簇集区（BCR）基因与酪氨酸蛋白激酶ABL1发生基因融合。在治疗过程中，由于出现耐药或无反应，应用了包括伊马替尼、尼洛替尼、达沙替尼和波纳替尼在内的不同治疗方案。荧光原位杂交（FISH）和二代测序（NGS）被用于描述细胞遗传学和分子异常，以阐明向AML的发展过程：观察到7号染色体缺失，以及原癌基因MET（p.T110I）和非受体型酪氨酸蛋白磷酸酶11（PTPN11，p.Q510L）基因变异频率的增加。本报告描述了一例临床病例的全面特征，该病例显示出多种与基因异常相关的治疗耐药性。
