Department of Laboratory Medicine, West China Hospital, Sichuan University Chengdu, Sichuan, People's Republic of China.
Arch Pathol Lab Med. 2012 Jan;136(1):84-9. doi: 10.5858/arpa.2010-0700-OA.
Constitutive activation of the FMS-like tyrosine kinase 3 (FLT3) receptor tyrosine kinase by internal tandem duplication (ITD) has been researched in patients with de novo acute myeloid leukemia (AML).
To study the patterns of FLT3-ITD in Chinese patients with AML.
A total of 207 patients with de novo AML were enrolled in the study. Genomic DNA was extracted from peripheral blood and polymerase chain reaction was performed. GeneScan was used to analyze the mutant to wild-type ratio. The sequencing of mutated genes was performed to confirm the mutation types and exclude false positives.
A total of 42 cases (20.3%) were associated with mutations. FLT3-ITD was found equally in AML subtypes M1 to M6. The level of the ITD allele was heterogeneous. GeneScan showed that the mutant to wild-type ratio ranged from 0.03 to 3.78 (median, 0.43). Patients with a high ratio had significantly lower cancer remission rates and shorter survival. They also showed distinct clinical features including higher white blood cell counts and higher CD7 and CD56 expression. The length of the duplicated fragment was 26 to 57 bp (median, 43 bp). Twenty-two cases (52%) had simple tandem duplications, while 20 other cases (48%) had an extra interval of 12 to 30 bp before the tandem duplications. A hexanucleotide consisting of GAAAAG was found exclusively in the intervals. Patients with this GAAAAG interval showed better survival. The ITD to wild-type ratio, gene pattern, and CD7 expression status appear to be independent prognostic indices for patients with AML.
Detection of FLT3 mutation is fast, easy, and inexpensive. The mutant to wild-type ratio is helpful for performing detailed risk stratification. DNA sequence analysis is more precise for confirming and evaluating the mutation pattern.
内部串联重复（ITD）导致 FMS 样酪氨酸激酶 3（FLT3）受体酪氨酸激酶组成性激活，已在初发急性髓系白血病（AML）患者中进行了研究。
研究中国 AML 患者中 FLT3-ITD 的模式。
共纳入 207 例初发 AML 患者，提取外周血基因组 DNA，进行聚合酶链反应，应用基因扫描分析突变型与野生型的比值，对突变基因进行测序以确定突变类型并排除假阳性。
共发现 42 例（20.3%）与突变相关。FLT3-ITD 在 AML 亚型 M1 至 M6 中发现率相同。ITD 等位基因水平呈异质性。基因扫描显示突变型与野生型比值范围为 0.03 至 3.78（中位数 0.43）。高比值患者的癌症缓解率显著降低，生存时间缩短，且具有明显的临床特征，包括白细胞计数较高和 CD7、CD56 表达较高。重复片段长度为 26 至 57bp（中位数 43bp）。22 例（52%）为单纯串联重复，20 例（48%）其他病例在串联重复前有 12 至 30bp 的额外间隔，该间隔仅存在 GAAAAG 六核苷酸。有此 GAAAAG 间隔的患者生存情况更好。FLT3 突变与野生型比值、基因模式和 CD7 表达状态似乎是 AML 患者的独立预后指标。
FLT3 突变检测快速、简便、经济，突变型与野生型比值有助于进行详细的风险分层，DNA 序列分析更精确地确认和评估突变模式。
