Tennant G B, Walsh V, Truran L N, Edwards P, Mills K I, Burnett A K
Department of Haematology, University of Wales College of Medicine, Cardiff, UK.
Br J Haematol. 2000 Dec;111(3):853-62.
Myelodysplastic syndromes (MDS) are characterized by a clonal disorder of haemopoiesis with defective growth in vitro. The long-term culture system was used to examine aspects of stromal function in MDS patients. Primary long-term cultures of MDS bone marrow showed poor myelopoiesis with progenitors being detected for a median 3.5 weeks (n = 12) compared with 18 weeks in cultures of normal marrow (n = 10; P < 0.0001). The haemopoietic function of adherent layers was assessed in secondary co-cultures seeded with 5 x 10(6) cord blood mononuclear cells on irradiated normal (n = 27; aged 38-82 years) or MDS (n = 32; aged 41-86 years) adherent layers (> 60% confluent). The median myeloid progenitor number/cord blood co-culture was 135 in 5-week-old cultures with normal adherent layers and 22 in those with MDS layers (P < 0.0001). Myeloid colonies were detectable for a median 11 weeks with normal adherent layers and 6 weeks with MDS adherent layers (P < 0.0001); erythroid colonies were detectable for 7 weeks (normal) compared with 5 weeks (MDS) (P < 0.01). The differences in granulocyte-macrophage colony forming unit (CFU-GM) generation were not related to patient age. Cells from adherent layers of at least half of the primary normal (n = 48) and MDS (n = 26) long-term cultures expressed cytokines [interleukin (IL)-3, IL-1 beta, thrombopoietin (Tpo) and erythropoietin (Epo)] and receptors for retinoic acid (RAR alpha) [IL-2, IL-3, macrophage colony stimulating factor (M-CSF) (Fms) and Tpo (Mpl)]. Only IL-1 beta expression was reduced in week-5 MDS cultures compared with those from normal marrows (P < 0.05). There was also a highly significant decline in IL-1 beta expression in normal (but not MDS) adherent layers between week 5 and week 10. Thus, the adherent layers in cultures grown from MDS patients were haemopoietically defective and showed abnormal IL-1 beta expression.
骨髓增生异常综合征（MDS）的特征是造血克隆性疾病，体外生长存在缺陷。长期培养系统用于研究MDS患者的基质功能。MDS骨髓的原代长期培养显示髓系造血功能差，祖细胞检测到的中位时间为3.5周（n = 12），而正常骨髓培养为18周（n = 10；P < 0.0001）。在接种5×10⁶脐血单个核细胞于经辐照的正常（n = 27；年龄38 - 82岁）或MDS（n = 32；年龄41 - 86岁）贴壁层（汇合度> 60%）的二次共培养中评估贴壁层的造血功能。5周龄培养物中，正常贴壁层的髓系祖细胞数/脐血共培养的中位数为135，MDS贴壁层为22（P < 0.0001）。正常贴壁层的髓系集落检测到的中位时间为11周，MDS贴壁层为6周（P < 0.0001）；红系集落检测到的时间正常为7周，MDS为5周（P < 0.01）。粒细胞 - 巨噬细胞集落形成单位（CFU - GM）生成的差异与患者年龄无关。至少一半的原代正常（n = 48）和MDS（n = 26）长期培养贴壁层细胞表达细胞因子[白细胞介素（IL）-3、IL - 1β、血小板生成素（Tpo）和促红细胞生成素（Epo）]以及维甲酸受体（RARα）[IL - 2、IL - 3、巨噬细胞集落刺激因子（M - CSF）（Fms）和Tpo（Mpl）]。与正常骨髓相比，第5周的MDS培养物中仅IL - 1β表达降低（P < 0.05）。在第5周和第10周之间，正常（而非MDS）贴壁层中的IL - 1β表达也有极显著下降。因此，MDS患者培养的贴壁层造血功能有缺陷，且IL - 1β表达异常。
