Department of Hematology and Oncology, Charité University School of Medicine, Berlin, Germany.
Leuk Lymphoma. 2013 Jan;54(1):145-52. doi: 10.3109/10428194.2012.704999. Epub 2012 Sep 5.
Mutation of the FMS-like tyrosine kinase-3 (FLT3) gene occurs with a frequency of 20-25% in acute myeloid leukemia (AML). Different studies have reported conflicting results, stating the importance of the length, position and number of internal tandem duplications (ITDs) for prognostic significance. In the present study, FLT3-ITD mutations were found in 51 (23%) of 218 patients with AML. Using sequence analysis we categorized ITD integration sites according to functional regions of the FLT3 receptor. Median ITD size was 61 bp. The insertion site was strongly correlated with ITD size: more C-terminal located inserted fragments were significantly bigger. Our data confirm that FLT3-ITD mutations identify a subset of young patients with AML with normal cytogenetics but with inferior outcome. Patients with AML with mutation localization outside the juxtamembrane domain showed no correlation with worse prognosis. A high mutant/wild-type ratio appears to have a major impact on the prognostic relevance.
FMS 样酪氨酸激酶-3（FLT3）基因突变在急性髓系白血病（AML）中的发生率为 20-25%。不同的研究报告了相互矛盾的结果，指出内部串联重复（ITD）的长度、位置和数量对预后意义重大。在本研究中，在 218 例 AML 患者中发现 51 例（23%）存在 FLT3-ITD 突变。通过序列分析，我们根据 FLT3 受体的功能区域对 ITD 整合位点进行了分类。中位 ITD 大小为 61bp。插入位点与 ITD 大小密切相关：位于 C 端的插入片段明显更大。我们的数据证实，FLT3-ITD 突变可确定具有正常细胞遗传学的年轻 AML 患者亚群，但预后较差。位于跨膜区以外的 AML 突变患者与预后不良无相关性。高突变/野生型比值似乎对预后有重大影响。
