检测 Waldenström 巨球蛋白血症和意义未明的单克隆免疫球蛋白血症患者外周血中的 MYD88 L265P。
Detection of MYD88 L265P in peripheral blood of patients with Waldenström's Macroglobulinemia and IgM monoclonal gammopathy of undetermined significance.
机构信息
1] Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, USA [2] Department of Medicine, Harvard Medical School, Boston, MA, USA.
Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, USA.
出版信息
Leukemia. 2014 Aug;28(8):1698-704. doi: 10.1038/leu.2014.65. Epub 2014 Feb 10.
MYD88 L265P is highly prevalent in Waldenstrom's Macroglobulinemia (WM) and IgM monoclonal gammopathy of unknown significance (MGUS). We investigated whether MYD88 L265P could be identified by peripheral blood (PB) allele-specific PCR. MYD88 L265P was detected in untreated WM (114/118; 96.6%); previously treated WM (63/102; 61.8%); and IgM MGUS (5/12; 41.7%) but in none of 3 hyper-IgM or 40 healthy individuals. Median PB MYD88 L265P ΔCt was 3.77, 7.24, 10.89, 12.33 and 14.07 for untreated WM, previously treated WM, IgM MGUS, hyper-IgM and healthy individuals, respectively (P<0.0001). For the 232 IgM MGUS and WM patients, PB MYD88 L265P ΔCt moderately correlated to bone marrow (BM) disease (r=-0.3553; P<0.0001), serum IgM (r=-0.3262; P<0.0001) and hemoglobin (r=0.3005; P<0.0001) levels. PB MYD88 L265P ΔCt and serum IgM correlated similarly with BM disease burden. For positive patients, PB MYD88 L265P ΔCt was <6.5 in 100/114 (88%) untreated WM, and >6.5 in 4/5 (80%) IgM MGUS patients (P=0.0034). Attainment of a negative PB MYD88 L265P mutation status was associated with lower BM disease (P=0.001), serum IgM (P=0.019) and higher hemoglobin (P=0.004) levels in treated patients. These studies show the feasibility for detecting MYD88 L265P by PB examination, and the potential for PB MYD88 L265P ΔCt use in the diagnosis and management of WM patients.
MYD88 L265P 在华氏巨球蛋白血症 (WM) 和意义未明的单克隆免疫球蛋白血症 (MGUS) 中高度普遍存在。我们研究了外周血 (PB) 等位基因特异性 PCR 是否可以识别 MYD88 L265P。在未经治疗的 WM（114/118；96.6%）、先前治疗的 WM（63/102；61.8%）和 IgM MGUS（5/12；41.7%）中检测到 MYD88 L265P，但在 3 例高 IgM 血症或 40 例健康个体中均未检测到。未经治疗的 WM、先前治疗的 WM、IgM MGUS、高 IgM 血症和健康个体的 PB MYD88 L265P ΔCt 中位数分别为 3.77、7.24、10.89、12.33 和 14.07（P<0.0001）。对于 232 例 IgM MGUS 和 WM 患者，PB MYD88 L265P ΔCt 与骨髓 (BM) 疾病（r=-0.3553；P<0.0001）、血清 IgM（r=-0.3262；P<0.0001）和血红蛋白（r=0.3005；P<0.0001）水平中度相关。PB MYD88 L265P ΔCt 与血清 IgM 与 BM 疾病负担的相关性相似。对于阳性患者，在 114 例未经治疗的 WM 患者中，PB MYD88 L265P ΔCt<6.5 的患者为 100/114（88%），而在 5 例 IgM MGUS 患者中>6.5 的患者为 4/5（80%）（P=0.0034）。在接受治疗的患者中，达到阴性 PB MYD88 L265P 突变状态与较低的 BM 疾病（P=0.001）、血清 IgM（P=0.019）和较高的血红蛋白（P=0.004）水平相关。这些研究表明，通过 PB 检查检测 MYD88 L265P 是可行的，并且 PB MYD88 L265P ΔCt 有潜力用于 WM 患者的诊断和管理。
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