Interdisciplinary Clinic for Stem Cell Transplantation, University Cancer Center Hamburg, Germany.
Clin Exp Med. 2010 Sep;10(3):205-8. doi: 10.1007/s10238-009-0058-9. Epub 2009 Jul 23.
The close association of the myeloproliferative neoplasms with the activating non-receptor tyrosine kinase JAK2V617F mutation is well established. To further clarify the pathomechanisms of this mutation in patients with myelofibrosis, we performed screening with quantitative real-time PCR for the respective mutation in in vitro expanded bone marrow (BM) mesenchymal stromal cells (MSCs) and compared the results with BM/peripheral blood (PB). Eight patients with primary/secondary myelofibrosis were investigated before (n = 4) or after allogeneic stem cell transplantation (n = 4). All patients had systemic evidence of the JAK2V617F mutation in BM/PB (mutation ratios 0.2-23.5) at the time of investigation in contrast to negative results in the MSCs (n = 7) or a very low (0.004) mutation ratio (n = 1) which was probably due to hematopoietic contamination. The four patients post-transplant had systemic donor chimerism between 96.5 and 100% in BM/PB, while MSCs showed no evidence of donor-specific alleles. In conclusion, in myelofibrosis, the JAK2V617F mutation is restricted to hematopoietic cells, and cannot explain the stromal alterations being observed in this disorder. Further, the MSCs remain of recipient origin after allogeneic SCT, which might contribute to the increased risk of graft dysfunction or failure in myelofibrosis patients after allogeneic transplantation.
骨髓增殖性肿瘤与激活的非受体酪氨酸激酶 JAK2V617F 突变密切相关。为了进一步阐明 JAK2V617F 突变在骨髓纤维化患者中的发病机制，我们使用实时定量 PCR 对体外扩增的骨髓（BM）间充质基质细胞（MSCs）中的相应突变进行了筛选，并将结果与 BM/外周血（PB）进行了比较。在调查时，8 例原发性/继发性骨髓纤维化患者中有 4 例处于未治疗状态，4 例接受了异基因干细胞移植。与 MSCs（n = 7）或非常低的突变率（n = 1）（可能由于造血细胞污染）的阴性结果相比，所有患者的 BM/PB 中均存在 JAK2V617F 突变的系统证据（突变率 0.2-23.5）。这四个移植后患者的 BM/PB 中存在 96.5%至 100%的供体嵌合体，而 MSCs 则没有供体特异性等位基因的证据。总之，在骨髓纤维化中，JAK2V617F 突变仅限于造血细胞，不能解释在该疾病中观察到的基质改变。此外，在异基因 SCT 后，MSCs 仍来源于受体，这可能导致骨髓纤维化患者在异基因移植后移植物功能障碍或失败的风险增加。
