Brada S, de Wolf J, Hendriks D, Esselink M, Ruiters M, Vellenga E
Department of Hematology, University Groningen, The Netherlands.
Blood. 1996 Jul 15;88(2):505-10.
In the present study, we analyzed the capacity of CD34+/CD36- sorted bone marrow cells of myelodysplasia patients (n = 4) to differentiate along the erythroid lineage in the presence of erythropoietin (Epo) and mast cell growth factor (MGF). Two subgroups could be identified. In 6 patients, a normal number of burst-forming units-erythroid (BFU-Es) were cultured from CD34+/CD36- sorted cells. Cells from these patients did have the capacity to differentiate to colony-forming units-erythroid (CFU-Es) progenitors in cell suspension cultures with Epo plus MGF followed by Epo in the culture assay. Moreover, the cells became CD34-/CD36+/gly-cophorin A (GpA)+ after 7 days of culture with Epo plus MGF, a pattern comparable to that of normal progenitors. In contrast, in 8 patients, a different pattern was observed. No BFU-Es or a low number of BFU-Es were cultured from the CD34+/CD36- sorted cell fraction that was, in most of the cases, incapable of differentiating to CFU-E progenitors. Flow cytometry of the sorted population showed that, after 7 days of culture with Epo plus MGF, a high proportion of CD34+/CD36- cells persisted, whereas a low proportion of cells became CD34-/CD36+/GpA+. The unresponsiveness is not caused by the used growth factor combination, because the addition of interleukin-3 did not correct the defect. Evi-1 expression was studied in 9 cases to show whether an aberrant Evi-1 expression correlates with a disturbed erythroid development. Evi-1 expression was shown in 4 of 9 cases, whereas 3 of 9 cases did have a disturbed erythroid differentiation. In summary, the results show that the defects in the erythroid development in a subpopulation of patients with myelodysplasia is localized at an early stage of the erythroid differentiation and is associated with the persistent expression of the CD34 antigen and, in some cases, with the expression of Evi-1.
在本研究中，我们分析了骨髓增生异常综合征患者（n = 4）经CD34+/CD36-分选的骨髓细胞在促红细胞生成素（Epo）和肥大细胞生长因子（MGF）存在的情况下沿红系谱系分化的能力。可识别出两个亚组。在6例患者中，从CD34+/CD36-分选的细胞中培养出正常数量的红系爆式集落形成单位（BFU-E）。这些患者的细胞在含有Epo加MGF的细胞悬液培养中，随后在培养试验中加入Epo，确实有能力分化为红系集落形成单位（CFU-E）祖细胞。此外，在用Epo加MGF培养7天后，细胞变为CD34-/CD36+/血型糖蛋白A（GpA）+，这一模式与正常祖细胞的模式相当。相比之下，在8例患者中，观察到了不同的模式。从CD34+/CD36-分选的细胞组分中未培养出BFU-E或培养出的BFU-E数量较少，在大多数情况下，这些细胞无法分化为CFU-E祖细胞。对分选群体的流式细胞术分析表明，在用Epo加MGF培养7天后，高比例的CD34+/CD36-细胞持续存在，而低比例的细胞变为CD34-/CD36+/GpA+。这种无反应性不是由所用的生长因子组合引起的，因为添加白细胞介素-3并不能纠正该缺陷。对9例患者研究了Evi-1表达，以表明异常的Evi-1表达是否与红系发育紊乱相关。9例中有4例显示Evi-1表达，而9例中有3例确实存在红系分化紊乱。总之，结果表明，骨髓增生异常综合征患者亚群中的红系发育缺陷定位于红系分化的早期阶段，与CD34抗原的持续表达相关，在某些情况下，还与Evi-1的表达相关。
