Lilakos K, Viniou N A, Mavrogianni D, Vassilakopoulos T P, Dimopoulou M N, Plata E, Angelopoulou M K, Variami E, Stavrogianni N, Liapi D, Xilouri I, Galanopoulos A, Ageloudi M, Panayiotidis P, Voulgarelis M, Rombos J, Meletis J, Yataganas X, Pangalis G A
First Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, The Greek AML Study Group, Athens, Greece.
Anticancer Res. 2006 Mar-Apr;26(2A):1201-7.
Activating mutations of the FLT3 receptor tyrosine kinase are common in acute promyelocytic leukemia (APL) but have uncertain prognostic significance. Information regarding FLT3 expression levels in APL without FLT3 mutations is lacking.
Using RT-PCR, mutation analysis of the FLT3 gene, regarding internal tandem duplications (ITDs) and codon 835-836 point mutations, was performed and real-time PCR was carried out to determine the level of FLT3 expression in 11 APL patients at diagnosis and 5 in haematological remission with molecularly detectable disease.
High levels of FLT3 transcript, at least a 10-fold increase compared to the normal controls, were found at diagnosis in all 3 mutated cases and in 2 patients without detectable FLT3 mutations.
FLT3 overexpression can be documented in patients without FLT3 mutations. These patients might benefit from treatment using specific FLT3 tyrosine kinase inhibitors. Larger studies are needed to evaluate the clinical and biological significance of FLT3 overexpression in the absence of FLT3 mutations.
FLT3受体酪氨酸激酶的激活突变在急性早幼粒细胞白血病(APL)中很常见,但预后意义尚不确定。缺乏关于无FLT3突变的APL中FLT3表达水平的信息。
采用逆转录聚合酶链反应(RT-PCR)对11例初诊APL患者和5例分子水平可检测到疾病的血液学缓解患者进行FLT3基因内部串联重复(ITD)和密码子835 - 836点突变的突变分析,并进行实时PCR以确定FLT3表达水平。
在所有3例突变病例以及2例未检测到FLT3突变的患者中,初诊时均发现FLT3转录本水平较高,与正常对照相比至少增加了10倍。
在无FLT3突变的患者中可记录到FLT3过表达。这些患者可能从使用特异性FLT3酪氨酸激酶抑制剂的治疗中获益。需要进行更大规模的研究来评估无FLT3突变时FLT3过表达的临床和生物学意义。