Okabe Seiichi, Tauchi Tetsuzo, Tanaka Yuko, Sakuta Juri, Ohyashiki Kazuma
Department of Hematology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.
J Hematol Oncol. 2015 Aug 4;8:97. doi: 10.1186/s13045-015-0190-9.
The BCR-ABL; breakpoint cluster region-Abelson point mutation T315I is resistant to ABL tyrosine kinase inhibitors. However, axitinib, a vascular endothelial growth factor receptor inhibitor, is effective against this mutation. In this study, we investigated axitinib activity against ponatinib-resistant cells and found that axitinib inhibited cellular growth and apoptosis in Ba/F3 T315I-mutant cells and T315I-mutant primary samples, but not in ponatinib-resistant Ba/F3 cells and primary samples. Thus, an alternative strategy may be required to improve the prognosis of Philadelphia-chromosome-positive leukemia patients harboring BCR-ABL point mutations.
BCR-ABL；断裂点簇集区-阿贝尔森点突变T315I对ABL酪氨酸激酶抑制剂耐药。然而，血管内皮生长因子受体抑制剂阿昔替尼对该突变有效。在本研究中，我们研究了阿昔替尼对泊那替尼耐药细胞的活性，发现阿昔替尼可抑制Ba/F3 T315I突变细胞和T315I突变原代样本中的细胞生长和凋亡，但对泊那替尼耐药的Ba/F3细胞和原代样本无效。因此，可能需要一种替代策略来改善携带BCR-ABL点突变的费城染色体阳性白血病患者的预后。
