Nussenzveig Roberto H, Pham Ha T, Perkins Sherrie L, Prchal Josef T, Agarwal Archana M, Salama Mohamed E
a Associated Regional University Pathologists (ARUP) Laboratories ;
b Department of Pathology ;
Leuk Lymphoma. 2016;57(6):1429-35. doi: 10.3109/10428194.2015.1091932. Epub 2015 Dec 23.
The frequency of co-existing JAK2(V617F)/MPL and JAK2(V617F)/JAK2 exon-12 mutations has not been previously investigated in MPNs. Poor survival was reported in primary myelofibrosis with low JAK2(V617F) allelic burden. However, mutational status of JAK2 exon-12 or MPL were not reported in these patients. This study developed a cost-effective multiplex high resolution melt assay that screens for mutations in JAK2 gene exons-12 and -14 ((V617F)) and MPL gene exon-10. Co-existing mutations with JAK2(V617F) were detected in 2.9% (6/208; two JAK2 exon-12 and four MPL exon-10) patient specimens with known JAK2(V617F) (allelic-burden range: 0.1-96.8%). Co-existing mutations were detected in specimens with < 12% JAK2(V617F) allelic burden. Current WHO guidelines do not recommend further testing once JAK2(V617F) mutation is detected in MPNs. The findings, however, indicate that quantification of JAK2(V617F) allele burden may be clinically relevant in MPNs and in those with low allelic burden additional testing for JAK2 exon-12 and MPL exon-10 mutation should be pursued.
骨髓增殖性肿瘤（MPNs）中JAK2（V617F）/MPL和JAK2（V617F）/JAK2外显子12共突变的频率此前尚未得到研究。据报道，JAK2（V617F）等位基因负荷低的原发性骨髓纤维化患者生存率较低。然而，这些患者中未报告JAK2外显子12或MPL的突变状态。本研究开发了一种经济高效的多重高分辨率熔解分析方法，用于筛查JAK2基因外显子12和14（V617F）以及MPL基因外显子10中的突变。在已知JAK2（V617F）（等位基因负荷范围：0.1 - 96.8%）的2.9%（6/208；两个JAK2外显子12突变和四个MPL外显子10突变）患者样本中检测到与JAK2（V617F）共存的突变。在JAK2（V617F）等位基因负荷<12%的样本中检测到共存突变。目前世界卫生组织（WHO）指南不建议在MPNs中一旦检测到JAK2（V617F）突变就进行进一步检测。然而研究结果表明JAK2（V617F）等位基因负荷的定量在MPNs中可能具有临床意义，对于那些等位基因负荷低的患者，应进一步检测JAK2外显子12和MPL外显子10的突变。
