Evidence that the JAK2 G1849T (V617F) mutation occurs in a lymphomyeloid progenitor in polycythemia vera and idiopathic myelofibrosis
Evidence that the JAK2 G1849T (V617F) mutation occurs in a lymphomyeloid progenitor in polycythemia vera and idiopathic myelofibrosis
复制标题
DOI：
10.1182/blood-2006-03-007146
复制
发表时间：
2007-01-01
期刊：
影响因子：
20.3
通讯作者：
Giraudier, Stephane
中科院分区：
文献类型：
--
作者：
Delhommeau, Francois;Dupont, Sabrina;Giraudier, Stephane
JAK2 V617F突变最近被描述为与多余细胞增多症（PV），特发性骨髓纤维化（IMF）和必需血小板血症相关的必不可少的致癌事件。在所有髓样谱系中都检测到了该突变，但尚未在淋巴样细胞中检测到。这就提出了一个问题，是否发生在真正的淋巴细胞祖细胞中。在这项工作中，我们研究了外周血细胞中的突变以及来自PV和IMF的B，T和天然杀手（NK）细胞的存在。我们检测到IMF患者的B和NK细胞中B和NK细胞中的JAK2 V617F突变，而PV患者中有少数患者。此外，在少数情况下，IMF患者突变了周围T细胞。随后可以在来自PV和IMF的B/NK/Myelold祖细胞中检测到突变（纯合或杂合），在IMF中得出的克隆的频率要高得多。使用胎儿胸体器官培养（FTOC）测定法，在源自IMF和PV CD34（+）细胞的所有T细胞级分中也检测到突变。这些结果表明，髓增生性疾病起源于真正的髓样/淋巴样祖细胞，但它们的表型与髓样谱系的下游选择性增殖优势有关。
The JAK2 V617F mutation has recently been described as an essential oncogenic event associated with polycythemia vera (PV), idiopathic myelofibrosis (IMF), and essential thrombocythemia. This mutation has been detected in all myeloid lineages but has not yet been detected in lymphoid cells. This raises the question whether this molecular event occurs in a true lymphomyeloid progenitor cell. In this work, we studied the presence of the mutation in peripheral blood cells and sorted B, T, and natural killer (NK) cells from PV and IMF. We detected the JAK2 V617F mutation in B and NK cells in approximately half the patients with IMF and a minority of those with PV. Moreover, in a few cases patients with IMF had mutated peripheral T cells. The mutation (homozygous or heterozygous) could be subsequently detected in B/NK/myelold progenitors from PV and IMF, with a much higher frequency in clones derived from IMF. Using the fetal thymus organ culture (FTOC) assay, the mutation was also detected in all T-cell fractions derived from IMF and PV CD34(+) cells. These results demonstrate that myeloproliferative disorders take their origin in a true myeloid/lymphoid progenitor cell but that their phenotype is related to a downstream selective proliferative advantage of the myeloid lineages.