Shimazaki K, Ohshima K, Suzumiya J, Kawasaki C, Kikuchi M
Department of Pathology, School of Medicine, Fukuoka University, Fukuoka, Japan.
Br J Haematol. 2000 Sep;110(3):584-90. doi: 10.1046/j.1365-2141.2000.02228.x.
The myelodysplastic syndromes (MDS) are a group of disorders characterized by peripheral pancytopenia despite normo- or hypercellular bone marrow. This is thought to be as a result of the apoptosis of haematopoietic bone marrow cells resulting in ineffective haematopoiesis. To clarify the relationship between prognosis and apoptosis and/or cell proliferation in the bone marrow, we studied 51 cases with MDS. Bone marrow biopsies were stained immunohistochemically for MIB-1 (marker for proliferating cells) and CD34 (marker for stem cells). Apoptosis was visualized by detection of DNA fragmentation using TdT incorporation of nucleotides on 3' ends of DNA (TUNEL technique) and expressed as the apoptotic rate. MDS patients included 32 with refractory anaemia (RA), one RA with ringed sideroblasts (RARS) patient, seven RA with excess of blasts (RAEB) patients, eight patients with RAEB in transformation (RAEB-t) and three patients with chronic myelomonocytic leukaemia (CMMoL). In addition, we also studied six cases with acute myeloid leukaemia (AML) arising from MDS (AML-MDS) and ten control subjects. Fatal pancytopenia was the cause of death in 19 out of 51 patients. The apoptotic rate was higher in MDS patients (5.5%) than in control subjects (0.6%) and AML-MDS patients (0.4%). The percentage of MIB-1 positive cells was higher in MDS and AML-MDS than in control. The percentage of CD34-positive cells was higher in AML-MDS, RAEB, RAEB-t and CMMoL patients than control subjects and RA patients. Our findings indicate the activation of both the proliferative and apoptotic rates in MDS. Poor prognosis correlated significantly with higher apoptotic rates, but not with percentages of MIB-1 and CD34-positive cells. Our results suggest that apoptosis might be a useful prognostic factor and inhibition of apoptotic mechanisms may induce leukaemic transformation in MDS.
骨髓增生异常综合征（MDS）是一组以骨髓细胞正常或增多但外周血细胞减少为特征的疾病。这被认为是造血骨髓细胞凋亡导致无效造血的结果。为了阐明骨髓中预后与凋亡和/或细胞增殖之间的关系，我们研究了51例MDS患者。骨髓活检标本采用免疫组织化学方法检测增殖细胞标志物MIB-1和干细胞标志物CD34。通过TdT介导的dUTP缺口末端标记法（TUNEL技术）检测DNA片段化来观察凋亡情况，并以凋亡率表示。MDS患者包括32例难治性贫血（RA）患者、1例环形铁粒幼细胞性难治性贫血（RARS）患者、7例原始细胞过多的难治性贫血（RAEB）患者、8例转变中的RAEB（RAEB-t）患者和3例慢性粒单核细胞白血病（CMMoL）患者。此外，我们还研究了6例由MDS转化而来的急性髓系白血病（AML-MDS）患者和10例对照者。51例患者中有19例死于严重全血细胞减少。MDS患者的凋亡率（5.5%）高于对照者（0.6%）和AML-MDS患者（0.4%）。MDS和AML-MDS患者中MIB-1阳性细胞的百分比高于对照者。AML-MDS、RAEB、RAEB-t和CMMoL患者中CD34阳性细胞的百分比高于对照者和RA患者。我们的研究结果表明MDS中增殖率和凋亡率均被激活。预后不良与较高的凋亡率显著相关，但与MIB-1和CD34阳性细胞的百分比无关。我们的结果提示凋亡可能是一个有用的预后因素，抑制凋亡机制可能诱导MDS发生白血病转化。
