Thiele J, Kvasnicka H M, Schmitt-Graeff A, Kriener S, Engels K, Staib P, Griesshammer M, Waller C F, Ottmann O G, Hansmann M-L
Institute of Pathology, University of Cologne, Cologne, Germany.
Histol Histopathol. 2004 Oct;19(4):1277-88. doi: 10.14670/HH-19.1277.
Preliminary data are available about bone marrow (BM) changes in patients with chronic myeloid leukemia (CML) who received the molecularly targeted and highly effective tyrosine kinase inhibitor Imatinib mesylate (STI571). This review is focused on a systematic assessment of BM features detectable at different stages of CML (stable, accelerated, blastic) following long-term (more than 10 months) treatment. By applying enzyme- and immunohistochemistry including monoclonal antibodies visualizing proliferating cell nuclear antigen (PCNA) and apoptosis (anti-apostatin), a more elaborate insight into alterations affecting hematopoiesis and the stroma compartment was gained. In patients with stable-phase CML therapy resulted in a significant reduction in cellularity, neutrophil granulopoiesis and number of megakaryocytes, accompanied by a retrieval of erythroid precursors. In patients with Imatinib as the only treatment morphometric analysis of CD61+ megakaryopoiesis was in keeping with a significant decrease in maturation defects implying a lesser amount of atypical micromegakaryocytes almost consistent with normalization. Moreover, a reduction of the initially enhanced (CD34+) microvessel density was detectable associated with a decrease in luminal distension. Regression of marked to moderate myelofibrosis was recognizable in about 70% of patients especially in the accelerated and blastic phases. The amount of myeloblasts, CD34+ progenitor cells and lysozyme-expressing immature myelomonocytic cells declined with treatment, but recurred in about 19% of patients that developed a leukemic relapse after 21+/-6 months of therapy. Data on proliferative activity and apoptosis in general supported in vitro findings concerning the inhibitory effect of this agent on growth associated with a tendency for stimulated apoptosis, at least in responding patients.
关于接受分子靶向高效酪氨酸激酶抑制剂甲磺酸伊马替尼（STI571）治疗的慢性髓性白血病（CML）患者骨髓（BM）变化的初步数据已经可得。本综述聚焦于对长期（超过10个月）治疗后CML不同阶段（稳定期、加速期、急变期）可检测到的BM特征进行系统评估。通过应用酶免疫组化和免疫组化，包括使用可视化增殖细胞核抗原（PCNA）和凋亡（抗凋亡素）的单克隆抗体，对影响造血和基质区室的改变有了更深入的了解。在稳定期CML患者中，治疗导致细胞数量、中性粒细胞生成和巨核细胞数量显著减少，同时红系前体细胞有所恢复。在仅接受伊马替尼治疗的患者中，对CD61 +巨核细胞生成的形态计量分析显示成熟缺陷显著减少，这意味着非典型微巨核细胞数量减少，几乎与正常化一致。此外，可检测到最初增强的（CD34 +）微血管密度降低，同时管腔扩张减小。约70%的患者，尤其是在加速期和急变期，明显至中度的骨髓纤维化出现消退。随着治疗，原始粒细胞、CD34 +祖细胞和表达溶菌酶的未成熟髓单核细胞数量减少，但在治疗21±6个月后发生白血病复发的约19%患者中又再次出现。关于增殖活性和凋亡的数据总体上支持了该药物对生长具有抑制作用并伴有刺激凋亡倾向的体外研究结果，至少在有反应的患者中是这样。
