Clinical significance of FLT3 in leukemia
Clinical significance of FLT3 in leukemia
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DOI：
10.1532/ijh97.05066
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发表时间：
2005-08-01
影响因子：
2.1
通讯作者：
Ozeki, K
中科院分区：
文献类型：
--
作者：
Kiyoi, H;Yanada, M;Ozeki, K
FLT 3与KIT、FMS和PDGFR一起是III类受体酪氨酸激酶。FLT 3突变首先被报道为质膜结构域编码序列的内部串联重复（FLT 3/ITD），随后被报道为激酶结构域内D835的错义突变（FLT 3/KDM）。此外，还发现了D835周围密码子的点突变、缺失和插入。FLT 3/ITD和FLT 3/KDM分别发生在15%至35%和5%至10%的AML患者中。因此，FLT 3突变是迄今为止在AML中报告的最常见的遗传改变。几项大规模研究已经证实FLT 3/ITD与白细胞增多和预后不良密切相关。尽管FLT 3/KDM的临床意义存在争议，但荟萃分析表明其对结局有不良影响。FLT 3/ITD在ALL患者中远不常见，而FLT 3/KDM在ALL患者中复发，特别是在那些携带MLL基因重排或超二倍体的患者中。FLT 3转录物的过表达已在一部分没有FLT 3突变的AML患者中得到证实，这与总体生存的不良预后相关。建议对FLT 3突变进行常规筛查，将患者分为不同的风险组，同时应进一步评估FLT 3突变患者的最佳治疗策略。
FLT3 is a class III receptor tyrosine kinase together with KIT, FMS and PDGFR. FLT3 mutations were first reported as internal tandem duplication (FLT3/ITD) of the juxtamembrane domain-coding sequence, and subsequently as a missense mutation of D835 (FLT3/KDM) within a kinase domain. Furthermore, point mutations, deletions, and insertions in the codons surrounding D835 have also been found. FLT3/ITD and FLT3/KDM occur in 15% to 35% and 5% to 10%, respectively, of patients with AML. FLT3 mutations are, therefore, the most frequent genetic alterations so far reported in AML. Several large-scale studies have confirmed that FLT3/ITD is strongly associated with leukocytosis and a poor prognosis. Although the clinical significance of FLT3/KDM is controversial, the meta-analysis suggests its adverse effect on the outcome. FLT3/ITD is far less common in patients with ALL, whereas FLT3/KDM is recurrently found in patients with ALL, especially in those harboring an MLL gene rearrangement or hyperdiploidy. The overexpression of FLT3 transcripts has been demonstrated in a proportion of the AML patients without FLT3 mutations, which are associated with a poor prognosis for overall survival. Routine screening of FLT3 mutations is recommended to stratify the patients into distinct risk groups, while the optimal treatment strategy for patients with FLT3 mutations should be further evaluated.