不同方法和标本检测华氏巨球蛋白血症患者MYD88突变的初步探索

OBJECTIVE: To improve the positivity rate and accuracy of MYD88 mutation detection in patients with Waldenström macroglobulinemia（WM）. METHODS: MYD88 mutation status was retrospectively evaluated in 66 patients diagnosed with WM in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from June 2017 to June 2021. The positivity rate and accuracy of the different methods and specimens for MYD88 mutation detection were analyzed. RESULTS: MYD88 mutations were detected in 51 of 66 patients with WM, with an overall positivity rate of 77％. The positivity rate of the next-generation sequencing（NGS）or allele-specific polymerase chain reaction（AS-PCR）was significantly higher than that of the first-generation Sanger sequencing（84％ vs 71％ vs 46％, P<0.05）. For the different specimens, the positivity rate for the lymph nodes or bone marrow was significantly higher than that of peripheral blood（79％ vs 84％ vs 52％, P<0.05）. The positivity rate of the MYD88 mutation in the lymph nodes, bone marrow, and peripheral blood determined by NGS was 86％, 90％, and 67％, respectively. The positivity rate in the lymph nodes, bone marrow, and peripheral blood detected by AS-PCR was 78％, 81％, and 53％, respectively. Thirty-nine patients with WM underwent ≥ 2 MYD88 mutation detections. The final MYD88 mutational status for each patient was used as the standard to determine the accuracy of the different methods and in different specimens. The accuracy of MYD88 mutation detection in the lymph nodes（n＝18）and bone marrow（n＝13）by NGS was significantly higher than that in the peripheral blood（n＝4）（100％ vs 100％ vs 75％, P<0.05）. There was no statistically significant difference in the accuracy of MYD88 mutation detection by AS-PCR in the lymph nodes（n＝15）, bone marrow（n＝11）, or peripheral blood（n＝16）（93％ vs 91％ vs 88％, P>0.05）. CONCLUSION: In the detection of the MYD88 mutation in patients diagnosed with WM, NGS or AS-PCR is more sensitive than Sanger sequencing. Lymph nodes and bone marrow specimens are better than peripheral blood specimens.