Alterations of the FLT3 gene in acute promyelocytic leukemia: association with diagnostic characteristics and analysis of clinical outcome in patients treated with the Italian AIDA protocol
Alterations of the FLT3 gene in acute promyelocytic leukemia: association with diagnostic characteristics and analysis of clinical outcome in patients treated with the Italian AIDA protocol
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DOI：
10.1038/sj.leu.2402723
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发表时间：
2002-11-01
期刊：
影响因子：
11.4
通讯作者：
Lo Coco, F
中科院分区：
文献类型：
--
作者：
Noguera, N;Breccia, M;Lo Coco, F
Flt3基因的改变，包括内部串联重复(ITDS)和D835突变，在急性髓系白血病中经常发生。我们调查了90例接受AIDA方案治疗的急性早幼粒细胞白血病(APL)患者的FLT3ITDS和D835突变的患病率和临床生物学相关性。对20例既有临床表现又有复发资料的患者进行了序贯分析。33例患者(37%)携带ITD，7例(7.7%)诊断时获得的原始细胞中存在D835突变。ITDS的存在与高WBC计数(P=0.0001)、M3变异(P=0.0004)和短(BR3)PML/RARα亚型(P=0.003)密切相关。ITD+Ve组和ITD-Ve组诱导反应无差异，但在分析无病生存期(DFS)和复发风险(RR)时，ITD+Ve组预后较差。然而，这些差异并未达到统计学意义。序贯研究显示了诊断和复发材料的不同模式，即ITD(-ve/-ve、+ve/+ve、+ve/-ve、-ve/+ve)和D835(-ve/-ve、+ve/-ve、-ve/+ve)。我们的结果表明，在APL中，Flt3的改变与更具侵袭性的临床特征有关，并提示这些损害可能在白血病进展中不起主要作用。
Alterations in the FLT3 gene, including internal tandem duplications (ITDs) and D835 mutations occur frequently in acute myelogenous leukemia. We investigated the prevalence and clinico-biological correlations of FLT3 ITDs and D835 mutations in 90 patients with acute promyelocytic leukemia (APL) receiving the AIDA protocol. Twenty patients in which both presentation and relapse material was available were analyzed sequentially. Thirty-three patients (37%) harbored the ITD, and seven (7.7%) the D835 mutation in blasts obtained at diagnosis. Presence of ITDs was strongly associated with high WBC count (P = 0.0001), M3 variant (P = 0.0004), and the short (BR3) PML/RARalpha isoform (P = 0.003). There was no difference in response to induction in the two ITD+ve and ITD-ve groups, while a trend towards inferior outcome was observed for ITD+ve cases when analyzing disease-free survival (DFS) and relapse risk (RR). These differences, however, did not reach statistical significance. Sequential studies showed variable patterns in diagnostic and relapse material, ie ITD (-ve/-ve, +ve/+ve, +ve/-ve, -ve/+ve) and D835 (-ve/-ve, +ve/-ve, -ve/+ve). Our results indicate that FLT3 alterations are associated in APL with more aggressive clinical features and suggest that these lesions may not play a major role in leukemia progression.