JAK2V617F allele burden discriminates essential thrombocythemia from a subset of prefibrotic-stage primary myelofibrosis
JAK2V617F allele burden discriminates essential thrombocythemia from a subset of prefibrotic-stage primary myelofibrosis
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DOI：
10.1016/j.exphem.2009.07.005
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发表时间：
2009-10-01
影响因子：
2.6
通讯作者：
Kreipe, Hans
中科院分区：
文献类型：
--
作者：
Hussein, Kais;Bock, Oliver;Kreipe, Hans
目的。在费城染色体阴性的骨髓增殖性肿瘤（Ph - MPN）中，原发性血小板增多症（ET）和原发性骨髓纤维化（PMF）的前纤维化阶段是两种有相当多重叠的亚型。
材料与方法。在本研究中，490例MPN病例的组织病理学分类与JAK2（V617F）和MPLW515L的等位基因负荷相关联。
结果。Ph - MPN各类型在JAK2（V617F）和MpL（W515L）等位基因负荷方面有很大重叠，但ET显示突变等位基因负荷＜40%的JAK2（V617F）等位基因（中位数为24%的JAK2（V617F）等位基因；n = 90；p＜0.001）。随访期间JAK2（V617F）等位基因的增加与纤维化或原始细胞进展无关，但与ET中的红细胞增多转变有关。在3%的ET和8%的PMF中发现了MPLW515L，纤维化PMF中突变等位基因的百分比显著高于前纤维化PMF（中位数为78%的MPLW515L等位基因；p＜0.05）。
结论。组织病理学分类ET和前纤维化PMF与JAK2（V617F）突变等位基因负荷有显著差异相关，但与MPLW515L无关，与JAK2（V617F）相反，MPLW515L在纤维化病例中的突变等位基因百分比高于前纤维化病例。因此，对于ET和前纤维化PMF是最可能诊断的Ph - MPN，JAK2（V617F）等位基因负荷＞50%更倾向于前纤维化PMF的诊断。（C）2009 ISEH -血液学与干细胞学会。由爱思唯尔公司出版。
Objective. Among Philadelphia chromosome-negative myeloproliferative neoplasms (Ph- MPN), essential thrombocythemia (ET) and the prefibrotic phase of primary myelofibrosis (PMF) represent two subtypes with considerable overlap.Materials and Methods. In this study, histopathological classification of 490 MPN cases was correlated with the allelic burden of JAK2(V617F) and MPLW515L.Results. Ph- MPN entities largely overlap with regard to JAK2(V617F) and MpL(W5151) allele burden, but ET displayed mutant allele burden 40% JAK2(V617F) alleles (median, 24% JAK2(V617F) alleles; n = 90; p < 0.001). Increase in JAK2(V617F) alleles during follow-up could not be linked to fibrosis or blastic progression but was related to polycythemic transformation in ET.MPLW515L was found in 3% of ET and 8% of PMF, with a significantly higher percentage of mutated alleles in fibrotic than prefibrotic PMF (median, 78% MPLW515L alleles; p < 0.05).Conclusion. Histopathological categories ET and prefibrotic PMF correlate with significant differences in mutant allelic burden of JAK2(V617F), but not of MPLW515L which, by contrast to JAK2(V617F), shows a higher percentage of mutated alleles in fibrotic than in prefibrotic cases. Thus, for Ph- MPN in which ET and prefibrotic PMF represent the most probable diagnoses, a JAK2(V617F) allele burden > 50% favors a diagnosis of prefibrotic PMF. (C) 2009 ISEH -Society for Hematology and Stem Cells. Published by Elsevier Inc.