We aimed to detect the MYD88^L265P and CXCR4^S338X mutations in cell-free DNA (cfDNA) in patients with Waldenström macroglobulinemia (WM). We collected peripheral blood and paired bone marrow aspirates from 27 WM patients (including 16 patients with newly diagnosed WM, 3 patients with WM in relapse and 8 patients with WM during treatment). cfDNA was extracted from peripheral blood using a QIAamp Circulating Nucleic Acid Kit. The MYD88^L265P and CXCR4^S338X mutations were detected by real-time allele-specific PCR (AS-PCR) in cfDNA and genomic DNA (gDNA) extracted from bone marrow aspirates. The sensitivity of real-time AS-PCR for detecting MYD88^L265P in cfDNA was determined using a serial dilution of 10%, 2%, 0.4% and 0.08% MYD88^L265P cfDNA in wild-type cfDNA. Among the 27 patients, MYD88^L265P was detected in 88.9% of them in gDNA and in 85.2% of them in cfDNA, with a concordance rate of 96.3%. The concordance rates were 93.8%, 100% and 100% in patients with newly diagnosed WM, patients with WM in relapse and patients with WM during treatment, respectively. The sensitivity of real-time AS-PCR for detecting MYD88^L265P in cfDNA was 0.4%. CXCR4^S338X was detected in 6.3% of the 16 newly diagnosed WM patients in both gDNA and cfDNA, with a concordance rate of 100.0%. It is feasible to apply cfDNA to detect MYD88^L265P and CXCR4^S338X in WM patients with a high concordance rate.

我们旨在检测Waldenström巨球蛋白血症（WM）患者无细胞DNA（cfDNA）中的MYD88 ^L265P和CXCR4 ^S338X突变。我们从27名WM患者（包括16名新诊断的WM患者，3例复发的WM患者和8例治疗期间的WM患者）中收集了外周血和成对的骨髓抽吸物。使用QIAamp循环核酸试剂盒从外周血中提取cfDNA。通过实时等位基因特异性PCR（AS-PCR）在cfDNA和从骨髓穿刺物中提取的基因组DNA（gDNA）中检测到MYD88 ^L265P和CXCR4 ^S338X突变。实时AS-PCR检测MYD88 ^{L265P的敏感性}使用在野生型cfDNA中的10％，2％，0.4％和0.08％MYD88 ^L265P cfDNA的系列稀释液确定cfDNA中的^cDNA含量。在27例患者中，在gDNA中检出MYD88 ^{L265P的比例}为88.9％，在cfDNA中检出MYD88 ^L265P的比例为96.3％。新诊断的WM患者，复发性WM患者和治疗期间WM患者的一致性率分别为93.8％，100％和100％。实时AS-PCR检测cfDNA中MYD88 ^{L265P的敏感性}为0.4％。在16名新诊断的WM患者中，在gDNA和cfDNA中均检测到6.3％的CXCR4 ^S338X，一致性率为100.0％。应用cfDNA检测MYD88 ^L265P和CXCR4 ^S338X是可行的 在具有较高一致性率的WM患者中。