急性髓系白血病患者外周血细胞中FLT3基因表达与FLT3／ITD突变的关系及其意义

背景与目的：研究表明FLT3／ITD突变的急性髓性白血病（acutemyeloid leukemia，AML）患者预后差，但关于AML患者FLT3基因的表达水平在预后中的作用及其与FLT3／ITD突变关系的研究尚不充分。本研究探讨初治AML患者FLT3基因的表达水平与FLT3／ITD突变的关系及其临床意义。方法：建立实时荧光定量PCR检测FLT3基因表达水平及PCR检测FLT3／ITD突变的方法。分析79例初治AML患者FLT3基因水平、FLT3／ITD突变及与预后的关系。结果：22．7％（18／79）的AML患者存在FLT3／ITD突变。92．4％（73／79）的患者标本中可检测到FLT3基因表达，FLT3基因表达水平为0-7320，中位数为312，正常对照组未检测到FLT3基因的表达。FLT3基因高表达及FLT3／ITD突变AML组的白细胞计数及骨髓白血病细胞均显著高于低表达和无突变AML组（P〈0．05）。FLT3基因高表达的AML组FLT3／ITD突变率（25．6％）同低表达的AML组（20．0％）相比，差异无统计学意义（P〉0．05），FLT3／ITD突变AML患者FLT3基因表达中位数与无突变组比较差异也无统计学意义。FLT3／ITD突变组的完全缓解率（58．8％）显著低于无FLT3／ITD突变组（82．1％）（P〈0．05）；FLT3基因高表达AML组FLT3／ITD的完全缓解率（68．6％）同低表达AML组（84．2％）相比差异无统计学意义（P〉0．05），但无FLT3／ITD突变组中，FLT3基因高表达组完全缓解率（69．2％）显著低于低表达组（93-3％）（P〈0．05）。结论：FLT3高表达与FLT3／ITD突变之间无明显相关性，FLT3高表达对于无FLT3／ITD突变AML患者可能是一个预后不良的指标。

Correlation of Fms-like tyrosine kinase 3 (FLT3) gene expression to FLT3/internal tandem duplication mutation in peripheral blood of acute myeloid leukemia

Background and Objective： Fins-like tyrosine kinase 3 internal tandem duplication （FLT3/ITD） is associated with an unfavorable prognosis in acute myeloid leukemia （AML）. However, the role of FLT3 expression as well as its correlation to FLT3/ITD has not sufficiently studied. This study was to evaluate the relationship between FLT3 gene expression and FLT3/ITD mutation in patients with de novo AML. Methods： FLT3 gene expression was determined by real-time quantitative polymerase chain reaction （RQ-PCR）. FLT3/ITD mutation was detected by PCR in 79 de novo AML patients. Results. FLT3/ITD mutations were found in 22.8% （18/79） patients. FLT3 gene expression （range. 0-7320, median. 312） was detected in 92.4% （73/ 79） patients, but not in normal controls. Compared to AML patients with low FLT3 expressers and without FLT3/ITD mutation, patients with high FLT3 expressers and FLT3/ITD mutation had a significantly higher white blood count as well as a higher ratio of bone marrow blasts. The positive rate of FLT3/ITD mutation was not correlated to the level of FLT3 expression, and no statistical difference of FLT3 expression was found between AML patients with and without FLT3/ITD mutation. The complete remission （CR） rate of AML patients with FLT3/ITD mutation （58.8%） was significance lower than that of those without FLT3/ITD mutation （82.1%）. In AML patients without FLT3/ITD mutation, the CR rate was significantly lower in patients with high FLT3 expressers （69.2%） than in those with low FLT3 expressers （93.3%）.Conclusion. The FLT3 expression is not associated with FLT3/ITD mutation. High-FLT3 expression may be a poor prognostic factor for AML patients without FLT3/ITE） mutation.