Kiladjian J J, Casadevall N, Vainchenker W, Fenaux P
Service d'hématologie clinique, hôpital Avicenne, université Paris-XIII, APHP, 125, rue de Stalingrad, 93000 Bobigny, France.
Pathol Biol (Paris). 2007 Mar;55(2):85-7. doi: 10.1016/j.patbio.2006.06.004. Epub 2006 Aug 9.
The first international meeting on V617F JAK2 mutation in myeloproliferative disorders (MPD) was held by the PV-Nord group on behalf of the French Society of Hematology and Paris 13 University on November 18, 2005, in Paris (France). Twelve speakers, including representatives of the three European groups who discovered the V617F JAK2 mutation and international experts in the field of Philadelphia-negative MPD, presented original biological and clinical data that allow better insight in the relevance of V617F JAK2 mutation in the pathogenesis and management of those diseases. The role of V617F JAK2 in cytokine receptors trafficking and signaling was described. Follow-up of transgenic mice expressing V617F JAK2 showed that they develop typical features of myelofibrosis. Comparisons of JAK2 mutational status to clonality of hematopoiesis in essential thrombocythemia on the one hand, and to activation of transcription factors in myelofibrosis with myeloid metaplasia on the other hand, suggest that JAK2 mutation could be a second genetic event in a subset of patients. Alternatively, other gene mutation(s) have to be found to explain the development of V617F-negative MPD. In large series of MPD patients presented, clinical characteristics of mutated and non-mutated patients were found different. Finally, the place of V617F JAK2 testing in the diagnosis and management of MPD was discussed.
2005年11月18日，北欧真性红细胞增多症研究小组代表法国血液学协会及巴黎第十三大学，在法国巴黎举办了关于骨髓增殖性疾病（MPD）中V617F JAK2突变的首次国际会议。12位发言者，包括发现V617F JAK2突变的三个欧洲研究小组的代表以及费城染色体阴性MPD领域的国际专家，展示了原创的生物学和临床数据，这些数据有助于更深入了解V617F JAK2突变在这些疾病的发病机制及治疗中的相关性。会上描述了V617F JAK2在细胞因子受体运输和信号传导中的作用。对表达V617F JAK2的转基因小鼠的跟踪研究表明，它们会出现典型的骨髓纤维化特征。一方面，将原发性血小板增多症中JAK2突变状态与造血克隆性进行比较；另一方面，将骨髓化生伴骨髓纤维化中转录因子的激活情况与之比较，结果表明JAK2突变可能是部分患者的第二个遗传事件。或者，必须找到其他基因突变来解释V617F阴性MPD的发病机制。在大量MPD患者病例中，发现突变患者与未突变患者的临床特征有所不同。最后，讨论了V617F JAK2检测在MPD诊断和治疗中的地位。
