Invernizzi Rosangela, Travaglino Erica, Benatti Chiara, Malcovati Luca, Della Porta Matteo, Cazzola Mario, Ascari Edoardo
Institute of Internal Medicine and Medical Oncology, University of Pavia, IRCCS Policlinico S. Matteo, Pavia, Italy.
Eur J Haematol. 2006 Jun;76(6):494-501. doi: 10.1111/j.0902-4441.2006.t01-1-EJH2588.x. Epub 2006 Mar 9.
We analyzed the expression of the inhibitor of apoptosis survivin by immunocytochemistry in bone marrow cells from patients with chronic myelomonocytic leukemia (CMML) to evaluate possible abnormalities in comparison with other myelodysplastic (MDS) and myeloproliferative syndromes, and to investigate a possible correlation between survivin expression and altered apoptosis or proliferation, or relevant laboratory and clinical findings. Thirty-four patients with CMML [18 MDS-CMML and 16 myeloproliferative disorder (MPD)-CMML], 90 with MDS, 41 with acute myeloid leukemia (AML), 19 with chronic MPD and 25 control subjects were studied. In normal samples survivin was never detectable. In CMML survivin levels higher than in MDS and AML (P < 0.0001), but similar to those found in MPD were observed. In CMML and MDS apoptosis was significantly higher compared to normal controls and all other subtypes of leukemias (P < 0.0001). Proliferation did not differ significantly in normal controls, MDS and CMML; the lowest levels were observed in AML and MPD (P < 0.0001). In CMML there was no correlation between survivin expression and blast cell percentage, apoptosis or proliferation, FAB or WHO subgroup. Proliferation was higher in MDS-CMML and tended to correlate with overall survival. CMML-2 cases with higher survivin expression showed higher evolution rate and shorter survival. In conclusion, CMML is characterized by high proliferation and apoptosis. Survivin overexpression, by disrupting the balance between cell proliferation/differentiation and apoptosis, may play an important role in its pathophysiology. The detection of survivin-deregulated expression may provide a useful tool for diagnosis, prognosis and a possible target for experimental treatments.
我们采用免疫细胞化学方法分析了慢性粒单核细胞白血病（CMML）患者骨髓细胞中凋亡抑制蛋白survivin的表达，以评估与其他骨髓增生异常综合征（MDS）和骨髓增殖性综合征相比可能存在的异常情况，并研究survivin表达与凋亡或增殖改变以及相关实验室和临床发现之间的可能相关性。研究了34例CMML患者[18例MDS-CMML和16例骨髓增殖性疾病（MPD）-CMML]、90例MDS患者、41例急性髓系白血病（AML）患者、19例慢性MPD患者和25例对照者。在正常样本中从未检测到survivin。在CMML中观察到survivin水平高于MDS和AML（P<0.0001），但与MPD中发现的水平相似。与正常对照和所有其他白血病亚型相比，CMML和MDS中的凋亡明显更高（P<0.0001）。正常对照、MDS和CMML中的增殖没有显著差异；AML和MPD中的增殖水平最低（P<0.0001）。在CMML中，survivin表达与原始细胞百分比、凋亡或增殖、FAB或WHO亚组之间没有相关性。MDS-CMML中的增殖较高，并且倾向于与总生存期相关。survivin表达较高的CMML-2病例显示出较高的进展率和较短的生存期。总之，CMML的特征是高增殖和高凋亡。Survivin的过表达通过破坏细胞增殖/分化与凋亡之间的平衡，可能在其病理生理学中起重要作用。检测survivin失调表达可能为诊断、预后提供有用工具，并可能成为实验性治疗的靶点。
