Auewarakul Chirayu U, Sritana Narongrit, Limwongse Chanin, Thongnoppakhun Wanna, Yenchitsomanus Pa-thai
Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Cancer Genet Cytogenet. 2005 Oct 15;162(2):127-34. doi: 10.1016/j.cancergencyto.2005.03.011.
FLT3 mutations have been reported to be the most frequent mutation in acute myeloid leukemia (AML). No data currently exist regarding FLT3 mutations in Southeast Asian patients. In this study, the incidence and type of FLT3 mutation in a large series of Thai AML patients were determined. FLT3 internal tandem duplication (ITD) mutations were observed in 24.6%, FLT3 tyrosine kinase domain mutations in 3.1%, and dual mutations in 2.7% of 256 newly diagnosed Thai AML patients. ITD mutations were mostly restricted to the juxtamembrane domain, and the in-frame ITD length varied from 21 to 201 base pairs. Six types of point mutations were identified, including Asp835Tyr, Asp835His, Asp835Glu, Asp835Ala, Ile836, and a novel mutation, Asp835Del/Ile836Val, which resulted in the loss of aspartic acid and substitution of isoleucine by valine. A rare leukemia karyotype, trisomy 11, was found to coexist with this novel FLT3 mutation, whereas the majority of patients with FLT3 mutations had a normal karyotype. Overall, FLT3 mutation was associated with a significantly higher white blood cell count and older age than the wild-type FLT3. In conclusion, the incidence of FLT3 mutation in Thailand is as high as that of western countries. The clinical significance of the novel mutation requires further studies in a larger population.
据报道，FLT3突变是急性髓系白血病（AML）中最常见的突变。目前尚无关于东南亚患者FLT3突变的数据。在本研究中，测定了一大系列泰国AML患者中FLT3突变的发生率和类型。在256例新诊断的泰国AML患者中，观察到FLT3内部串联重复（ITD）突变的发生率为24.6%，FLT3酪氨酸激酶结构域突变的发生率为3.1%，双重突变的发生率为2.7%。ITD突变大多局限于近膜结构域，框内ITD长度从21到201个碱基对不等。鉴定出六种点突变类型，包括Asp835Tyr、Asp835His、Asp835Glu、Asp835Ala、Ile836，以及一种新的突变Asp835Del/Ile836Val，该突变导致天冬氨酸缺失和异亮氨酸被缬氨酸取代。发现一种罕见的白血病核型，即11号染色体三体，与这种新的FLT3突变共存，而大多数FLT3突变患者的核型正常。总体而言，与野生型FLT3相比，FLT3突变与显著更高的白细胞计数和更高的年龄相关。总之，泰国FLT3突变的发生率与西方国家一样高。这种新突变的临床意义需要在更大规模的人群中进一步研究。
