Hussein Kais, Bock Oliver, Theophile Katharina, von Neuhoff Nils, Buhr Thomas, Schlué Jerome, Büsche Guntram, Kreipe Hans
Institute of Pathology, Hannover Medical School, 30625 Hannover, Germany.
Exp Hematol. 2009 Oct;37(10):1186-1193.e7. doi: 10.1016/j.exphem.2009.07.005. Epub 2009 Jul 17.
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.
In this study, histopathological classification of 490 MPN cases was correlated with the allelic burden of JAK2(V617F) and MPL(W515L).
Ph(-) MPN entities largely overlap with regard to JAK2(V617F) and MPL(W515L) allele burden, but ET displayed mutant allele burden <50%. PMF with different stages of myelofibrosis all yielded similar JAK2(V617F) allele burden. At initial presentation one-quarter of prefibrotic PMF cases exhibited an allele burden exceeding 50% (38% median JAK2(V617F) alleles, n=102). In ET, its main differential diagnosis, not a single case was found with >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. MPL(W515L) 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% MPL(W515L) alleles; p<0.05).
Histopathological categories ET and prefibrotic PMF correlate with significant differences in mutant allelic burden of JAK2(V617F), but not of MPL(W515L) 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.
在费城染色体阴性骨髓增殖性肿瘤（Ph(-) MPN）中，原发性血小板增多症（ET）和原发性骨髓纤维化（PMF）的纤维化前期代表了两种有相当重叠的亚型。
在本研究中，对490例MPN病例的组织病理学分类与JAK2(V617F)和MPL(W515L)的等位基因负担进行了关联分析。
Ph(-) MPN实体在JAK2(V617F)和MPL(W515L)等位基因负担方面有很大重叠，但ET显示突变等位基因负担<50%。不同骨髓纤维化阶段的PMF均产生相似的JAK2(V617F)等位基因负担。在初次就诊时，四分之一的纤维化前期PMF病例表现出等位基因负担超过50%（JAK2(V617F)等位基因中位数为38%，n = 102）。在ET（其主要鉴别诊断疾病）中，未发现一例JAK2(V617F)等位基因>40%的病例（JAK2(V617F)等位基因中位数为24%；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中的红细胞增多症转化有关。在3%的ET和8%的PMF中发现了MPL(W515L)，纤维化PMF中突变等位基因的百分比显著高于纤维化前期PMF（MPL(W515L)等位基因中位数为78%；p<0.05）。
组织病理学分类ET和纤维化前期PMF与JAK2(V617F)突变等位基因负担的显著差异相关，但与MPL(W515L)无关，与JAK2(V617F)相反，MPL(W515L)在纤维化病例中的突变等位基因百分比高于纤维化前期病例。因此，对于最可能诊断为ET和纤维化前期PMF的Ph(-) MPN，JAK2(V617F)等位基因负担>50%有利于诊断为纤维化前期PMF。
