Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
Blood. 2011 Jun 30;117(26):6987-90. doi: 10.1182/blood-2011-03-340273. Epub 2011 May 17.
Acute myeloid leukemia with a FLT3 internal tandem duplication (FLT3/ITD) mutation is an aggressive hematologic malignancy with a generally poor prognosis. It can be successfully treated into remission with intensive chemotherapy, but it routinely relapses. At relapse, the blasts tend to have higher mutant allelic ratios and, in vitro, are more addicted to the aberrant signaling from the FLT3/ITD oncoprotein. They remain highly responsive to FLT3 ligand, the levels of which rise several-fold during the course of chemotherapy. The question now arises as to whether these high levels of FLT3 ligand are actually promoting relapse, and, if so, how we can use this information to adjust our therapeutic approach and improve the cure rate for acute myeloid leukemia with FLT3/ITD.
FLT3 内部串联重复（FLT3/ITD）突变的急性髓系白血病是一种侵袭性血液恶性肿瘤，一般预后较差。虽然可以通过强化化疗成功缓解，但通常会复发。复发时，白血病细胞的突变等位基因比例往往更高，并且在体外对 FLT3/ITD 致癌蛋白的异常信号更为依赖。它们仍然对 FLT3 配体高度敏感，在化疗过程中其水平会升高数倍。现在的问题是，这些高水平的 FLT3 配体是否真的促进了复发，如果是，我们如何利用这些信息来调整治疗方法，提高 FLT3/ITD 急性髓系白血病的治愈率。
