Laboratory for Leukemia Diagnostics Department of Medicine III, University Hospital Munich, Campus Grosshadern Marchioninistr. 15, 81377 Munich, Germany.
Ann Hematol. 2012 Jan;91(1):9-18. doi: 10.1007/s00277-011-1280-6. Epub 2011 Jul 9.
Prognosis of AML in elderly patients is poor due to adverse patient characteristics and comorbidities. In addition, disease-associated parameters reveal differences between older and younger patients with AML. Survival in normal karyotype AML (NK-AML) is influenced by different clinical and molecular markers. The aim of this work was to investigate the frequencies of molecular markers in patients with NK-AML with a focus on NPM1 mutations and FLT3-ITD in different age groups. In the present study, we analyzed the frequencies of mutations of NPM1 and FLT3-ITD in a cohort of 1,321 adult patients and 148 children with AML treated within the AMLCG99, the AML98, and AML04 trials and their distribution in different age groups. Additionally, the frequencies of mutations in CEBPA genes, FLT3-TKD, and MLL-PTD were analyzed in the cohort with NK-AML (n = 729). Our data show that the presence of mutations of NPM1 (from 60% to 40%) and FLT3-ITD (from 50% to 20%) significantly decreased with age in adult AML. Consequently, the proportion of NPM1-/FLT3-ITD- patients increased with age. The decreasing frequency of NPM1 mutations in elderly patients was paralleled by a reduced complete remission (CR) rate in the elderly of 55% compared to 80% in the younger patients. By contrast, the frequencies of other gene mutations, like FLT3-TKD and MLL-PTD, and mutations in CEBPA were not age-dependent. The decreasing frequency of the favorable NPM1 mutations with increasing age may partially explain the worse outcome in the elderly patients. Furthermore, the increasing amount of elderly patients without NPM1 mutations or FLT3-ITD suggests that other molecular and clinical risk factors may influence prognosis in this age group.
由于患者特征和合并症不良，老年患者的 AML 预后较差。此外，疾病相关参数揭示了 AML 老年患者和年轻患者之间的差异。正常核型 AML（NK-AML）的生存受不同的临床和分子标志物影响。本工作旨在研究 NK-AML 患者中不同年龄组 NPM1 突变和 FLT3-ITD 等分子标志物的频率。在本研究中，我们分析了在 AMLCG99、AML98 和 AML04 试验中治疗的 1321 例成年患者和 148 例儿童 AML 患者队列中 NPM1 和 FLT3-ITD 突变的频率及其在不同年龄组中的分布。此外，还分析了 NK-AML 患者队列中 CEBPA 基因突变、FLT3-TKD 和 MLL-PTD 的频率（n=729）。我们的数据表明，成年 AML 中 NPM1 突变（从 60%降至 40%）和 FLT3-ITD 突变（从 50%降至 20%）的存在随年龄显著降低。因此，NPM1-/FLT3-ITD-患者的比例随年龄增加而增加。老年患者 NPM1 突变频率降低与老年患者完全缓解（CR）率从 80%降至 55%相对应。相比之下，FLT3-TKD 和 MLL-PTD 等其他基因突变的频率以及 CEBPA 基因突变与年龄无关。随着年龄的增加，有利的 NPM1 突变频率降低可能部分解释了老年患者预后较差的原因。此外，越来越多的老年患者没有 NPM1 突变或 FLT3-ITD，这表明其他分子和临床危险因素可能影响该年龄组的预后。
