Loss or Inhibition of Stromal-Derived PIGF Prolongs Survival of Mice with Imatinib-Resistant Bcr-Abl1+ Leukemia
Loss or Inhibition of Stromal-Derived PIGF Prolongs Survival of Mice with Imatinib-Resistant Bcr-Abl1+ Leukemia
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DOI：
10.1016/j.ccr.2011.05.007
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发表时间：
2011-06-14
期刊：
影响因子：
50.3
通讯作者：
Carmeliet, Peter
中科院分区：
文献类型：
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作者：
Schmidt, Thomas;Masouleh, Behzad Kharabi;Carmeliet, Peter
伊马替尼彻底改变了BCR-ABL 1（+）慢性粒细胞白血病（CML）的治疗，但是，在大多数患者中，尽管持续治疗，一些白血病细胞仍然存在，而另一些则变得耐药。在这里，我们报告说，PIGF水平升高，在CML和PIGF产生的骨髓基质细胞（BMSC）的病情严重程度。CML细胞通过诱导BMSC上调PIGF来培育其自身生长的土壤，PIGF不仅刺激BM血管生成，而且促进CML增殖和代谢，部分独立于BCR-ABL 1信号传导。抗PIGF治疗降低伊马替尼敏感和耐药CML小鼠的存活率，并增加伊马替尼的抗CML活性。这些结果可能需要进一步研究PIGF抑制对（伊马替尼耐药）CML的治疗潜力。
Imatinib has revolutionized the treatment of BCR-ABL1(+) chronic myeloid leukemia (CML), but, in most patients, some leukemia cells persist despite continued therapy, while others become resistant. Here, we report that PIGF levels are elevated in CML and that PIGF produced by bone marrow stromal cells (BMSCs) aggravates disease severity. CML cells foster a soil for their own growth by inducing BMSCs to upregulate PIGF, which not only stimulates BM angiogenesis, but also promotes CML proliferation and metabolism, in part independently of BCR-ABL1 signaling. Anti-PIGF treatment prolongs survival of imatinib-sensitive and -resistant CML mice and adds to the anti-CML activity of imatinib. These results may warrant further investigation of the therapeutic potential of PIGF inhibition for (imatinib-resistant) CML.