Institut für Pathologie, Universitätsmedizin Mainz, Langenbeckstr. 1, 55101 Mainz, Germany.
Virchows Arch. 2011 Nov;459(5):521-7. doi: 10.1007/s00428-011-1154-2. Epub 2011 Oct 18.
The JAK2-V617F mutation is prevalent in almost all patients with polycythemia vera (PV) and about half of the cases of essential thrombocythaemia (ET) and primary myelofibrosis (PMF). A different allele burden in these entities has long been noticed, but little is known about its distribution among the neoplastic hematopoietic cell lineages within the bone marrow. We conducted a microdissection study of JAK2-V617F-mutated myeloproliferative neoplasms (MPN); 10 cases each of ET, PV, and PMF, with separate analysis of the JAK2 mutation status in three hematopoietic cell lines (i.e., megakaryo-, granulo-, and erythropoiesis). Different numbers of cell lineages harboring the JAK2-V617F mutation were found, being the lowest in ET (17/30), higher in PV (24/30) and in PMF (22/30). The megakaryopoiesis was the most commonly mutated cell lineage (24/30 cases). By analyzing microdissectates we were able to demonstrate a different allele burden of the JAK2-V617F mutation in the megakaryo-, erythro-, and granulopoiesis within the bone marrow of a given case of MPN. We demonstrated differences in the number of mutated cell lineages. The different mutation status may contribute to the different phenotypes of ET, PV, and PMF.
JAK2-V617F 突变几乎普遍存在于所有真性红细胞增多症 (PV) 患者和约半数原发性血小板增多症 (ET) 和原发性骨髓纤维化 (PMF) 患者中。长期以来，人们已经注意到这些实体之间存在不同的等位基因负担，但对其在骨髓中肿瘤性造血细胞谱系中的分布知之甚少。我们对 JAK2-V617F 突变的骨髓增殖性肿瘤 (MPN) 进行了显微切割研究；每个 ET、PV 和 PMF 各有 10 例，并分别分析了三个造血细胞谱系中的 JAK2 突变状态（即巨核细胞、粒细胞和红细胞生成）。发现存在 JAK2-V617F 突变的造血细胞谱系数量不同，ET 最低（17/30），PV 和 PMF 较高（24/30 和 22/30）。巨核细胞生成是最常见的突变细胞谱系（24/30 例）。通过分析显微切割物，我们能够证明在给定 MPN 病例的骨髓中，JAK2-V617F 突变的等位基因负担在巨核细胞、红细胞和粒细胞生成中存在差异。我们证明了突变细胞谱系数量的差异。不同的突变状态可能导致 ET、PV 和 PMF 的不同表型。
