Hussein Kais, Stucki-Koch Angelika, Alchalby Haefaa, Triviai Ioanna, Kröger Nicolaus, Kreipe Hans
Institute of Pathology, Hannover Medical School, Hannover, Germany.
Institute of Pathology, Hannover Medical School, Hannover, Germany.
Biol Blood Marrow Transplant. 2016 Apr;22(4):644-650. doi: 10.1016/j.bbmt.2015.12.006. Epub 2015 Dec 19.
The only curative therapy for primary myelofibrosis (PMF) is allogeneic stem cell transplantation (ASCT). However, although we know that patients can benefit from ASCT, we do not know the extent of the changes of the expression profile of cytokines and matrix modulation factors. In this first systematic analysis, we evaluated the expression profile of 103 factors before and after transplantation to identify potential biomarkers. The expression of fibrosis-, inflammation-, and angiogenesis-associated genes was analyzed in a total of 52 bone marrow biopsies: PMF patients (n = 14) before and after ASCT and, for control purposes, post-ASCT multiple myeloma patients (n = 14) and non-neoplastic hematopoiesis (n = 10). In post-ASCT PMF cases, decreased expression of tissue inhibitor of metalloproteinases (TIMP) and platelet-derived growth factor alpha (PDGFA) correlated with bone marrow remodeling and hematological remission. Expression of several other matrix factors remained at high levels and may contribute to post-ASCT remodeling. This is the first systematic analysis of cytokine expression in post-ASCT PMF bone marrow that shows that normalization of bone marrow microenvironment is paralleled by decreased expression of TIMP and PDGFA.
原发性骨髓纤维化(PMF)的唯一治愈性疗法是异基因干细胞移植(ASCT)。然而,尽管我们知道患者可从ASCT中获益,但我们并不清楚细胞因子和基质调节因子表达谱的变化程度。在这项首次系统性分析中,我们评估了移植前后103种因子的表达谱,以确定潜在的生物标志物。在总共52份骨髓活检样本中分析了与纤维化、炎症和血管生成相关基因的表达:ASCT前后的PMF患者(n = 14),以及作为对照的ASCT后的多发性骨髓瘤患者(n = 14)和非肿瘤性造血样本(n = 10)。在ASCT后的PMF病例中,基质金属蛋白酶组织抑制剂(TIMP)和血小板衍生生长因子α(PDGFA)的表达降低与骨髓重塑和血液学缓解相关。其他几种基质因子的表达仍处于高水平,可能有助于ASCT后的重塑。这是对ASCT后PMF骨髓中细胞因子表达的首次系统性分析,表明骨髓微环境的正常化与TIMP和PDGFA表达的降低同时出现。