Mueller Susanne, Holdenrieder Stefan, Stieber Petra, Haferlach Torsten, Schalhorn Andreas, Braess Jan, Nagel Dorothea, Seidel Dietrich
Institute of Clinical Chemistry, University Hospital Munich-Grosshadern, Marchioninistr, 15, D-81377 Munich, Germany.
BMC Cancer. 2006 May 30;6:143. doi: 10.1186/1471-2407-6-143.
Elevated levels of nucleosomal DNA fragments can be detected in plasma and sera of patients with malignant diseases.
We investigated the course of nucleosomal DNA, thymidine kinase, lactate dehydrogenase and leukocytes in sera of 25 patients with acute myeloid leukemia during the first cycle of induction chemotherapy and tested their power to distinguish between patients with complete remission and those with no remission.
Almost all patients showed strongly decreasing levels of nucleosomal DNA during the first week, in some cases after initial peaks. In overall analysis of variance, DNA levels could clearly distinguish between patients with complete remission, who had higher DNA values, and those with insufficient response (p = 0.017). The area under the curve of DNA values of days 2-4 after start of therapy (AUC 2-4) discriminated between both groups with a sensitivity of 56% at a specificity of 100%. Further, pretherapeutic levels and AUC 2-4 of nucleosomal DNA correlated significantly with blast reduction after 16 days. A tendency to higher levels in patients with complete response was also found for thymidine kinase, lactate dehydrogenase and leukocytes, however the difference did not reach the level of significance (p = 0.542, p = 0.260, and p = 0.144, respectively).
Our results indicate that nucleosomal DNA fragments are valuable markers for the early prediction of therapeutic efficacy in patients with acute myeloid leukemia.
在恶性疾病患者的血浆和血清中可检测到核小体DNA片段水平升高。
我们调查了25例急性髓系白血病患者在诱导化疗第一周期血清中核小体DNA、胸苷激酶、乳酸脱氢酶和白细胞的变化过程,并测试了它们区分完全缓解患者和未缓解患者的能力。
几乎所有患者在第一周内核小体DNA水平都大幅下降,有些患者在最初出现峰值后下降。在总体方差分析中,DNA水平能够清晰地区分完全缓解患者(其DNA值较高)和反应不佳的患者(p = 0.017)。治疗开始后第2 - 4天DNA值的曲线下面积(AUC 2 - 4)在两组之间具有区分能力,敏感性为56%,特异性为100%。此外,核小体DNA的治疗前水平和AUC 2 - 4与16天后原始细胞减少显著相关。在完全缓解的患者中,胸苷激酶、乳酸脱氢酶和白细胞水平也有升高的趋势,但差异未达到显著水平(分别为p = 0.542、p = 0.260和p = 0.144)。
我们的结果表明,核小体DNA片段是急性髓系白血病患者治疗疗效早期预测的有价值标志物。