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首页> 外文期刊>Open Journal of Blood Diseases >Sunitinib Reduces Acute Myeloid Leukemia Clonogenic Cells in Vitro and Has Potent Inhibitory Effect on Sorted AML ALDH+ Cells
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Sunitinib Reduces Acute Myeloid Leukemia Clonogenic Cells in Vitro and Has Potent Inhibitory Effect on Sorted AML ALDH+ Cells

机译：舒尼替尼可减少急性髓样白血病克隆细胞的体外，并对分选的AML ALDH +细胞具有有效的抑制作用

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Sunitinib is an orally administered, multi-target tyrosine kinase inhibitor that has been approved by the FDA for the treatment of renal cell carcinoma and imatinib resistant gastro-intestinal tumors. Anti-leukemic activity of sunitinib has been examined in early clinical trials with limited success. However, recent trials on acute myeloid leukemia (AML) patients carrying FLT3 mutations have shown promising results. Effects of sunitinib on leukemic clonogenic cells and potential leukemic stem cells have not been examined so far. We analyzed the anti-proliferative and apoptotic properties of sunitinib on AML-derived cell lines. We also tested the effect of sunitinib on AML patient derived clonogenic cells (AML-CFC), as well as flow-sorted potential leukemic progenitors. Peripheral blood or bone marrow samples were obtained from newly diagnosed AML patients and flow sorted for CD34+ CD133+ or ALDH+ cells. Umbilical cord blood derived CD34+ cells were used as normal controls. Sunitinib induced growth arrest and apoptosis in AML derived cell lines. In addition, 7 μM sunitinib induced 75% reduction of AML-CFC as compared to DMSO treated control (±6.79%; n = 4). In contrast, 7 μM sunitinib treatment of umbilical cord blood derived normal CD34+ cells showed 29% reduction in AML-CFC (±6.77%; n = 5). Treatment of ALDH+ cells sorted from 2 AML cases and CD34+ CD133+ cells from one patient showed reduction of AML-CFC on treatment with sunitinib. Our study highlighted a potent anti-proliferative and proapoptotic effect of sunitinib on AML cell lines, AML patient derived clonogenic cells and potential leukemic stem cells.
机译：舒尼替尼是一种口服给药的多靶酪氨酸激酶抑制剂，已被FDA批准用于治疗肾细胞癌和伊马替尼耐药的胃肠道肿瘤。舒尼替尼的抗白血病活性已在早期临床试验中进行了测试，但收效甚微。但是，最近对携带FLT3突变的急性髓细胞白血病（AML）患者进行的试验显示出可喜的结果。迄今为止尚未研究舒尼替尼对白血病克隆细胞和潜在白血病干细胞的影响。我们分析了舒尼替尼对AML衍生细胞系的抗增殖和凋亡特性。我们还测试了舒尼替尼对AML患者衍生克隆细胞（AML-CFC）以及按流分类的潜在白血病祖细胞的作用。从新诊断的AML患者中获取外周血或骨髓样品，并按流分选CD34 + CD133 +或ALDH +细胞。脐带血来源的CD34 +细胞用作正常对照。舒尼替尼在AML衍生的细胞系中诱导生长停滞和凋亡。此外，与DMSO处理的对照组相比，舒尼替尼7μM诱导的AML-CFC降低了75％（±6.79％; n = 4）。相比之下，舒尼替尼对脐血来源的正常CD34 +细胞进行7μM处理后，AML-CFC降低了29％（±6.77％; n = 5）。用舒尼替尼治疗后，从2例AML病例中筛选出的ALDH +细胞和一名患者的CD34 + CD133 +细胞的治疗均显示出AML-CFC减少。我们的研究强调了舒尼替尼对AML细胞系，AML患者来源的克隆细胞和潜在的白血病干细胞具有有效的抗增殖和凋亡作用。

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