Saitoh K, Miura I, Takahashi N, Miura A B
Third Department of Internal Medicine, Akita University School of Medicine, Akita, Japan.
Blood. 1998 Oct 15;92(8):2886-92.
Myelodysplastic syndrome (MDS) is believed to be a stem-cell disorder involving cytopenia and dysplastic changes in three hematopoietic lineages. However, the involvement of pluripotent stem cells and progenitor cells has not been clarified conclusively. To address this issue, we used fluorescence in situ hybridization (FISH) of blood and bone marrow (BM) smears for mature cells and FISH of cells sorted by fluorescence-activated cell sorting for progenitor cells. Seven patients with MDS associated with trisomy 8 were studied. FISH showed +8 in granulocytes, monocytes, and erythroblasts, but not in lymphocytes. Sorted cells of T (CD3(+)), B (CD19(+)), and NK cells (CD3(-)CD56(+)) from peripheral blood did not contain +8, nor did CD34(+) subpopulations from BM including B (CD34(+)CD19(+)), T/NK (CD34(+)CD7(+)) progenitors, and pluripotent stem cells (CD34(+)Thy1(+)). The +8 chromosome abnormality was identified in stem cells only at the level of colony-forming unit of granulocyte-erythrocyte-macrophage-megakaryocyte (CFU-GEMM; CD34(+)CD33(+)). It may thus be concluded that cells affected by trisomy 8 in the context of MDS are at the CFU-GEMM level and that cells of lymphoid lineage are not involved. These results provide new insights into the biology of MDS and suggest that intensive chemotherapy and autologous BM transplantation may become important therapeutic strategies.
骨髓增生异常综合征（MDS）被认为是一种干细胞疾病，涉及血细胞减少和三个造血谱系的发育异常变化。然而，多能干细胞和祖细胞的受累情况尚未得到最终明确。为了解决这个问题，我们对成熟细胞的血液和骨髓涂片进行荧光原位杂交（FISH），对祖细胞进行荧光激活细胞分选法分选细胞的FISH。研究了7例与8号染色体三体相关的MDS患者。FISH显示粒细胞、单核细胞和成红细胞中有+8，但淋巴细胞中没有。外周血中T（CD3(+)）、B（CD19(+)）和NK细胞（CD3(-)CD56(+)）的分选细胞不含+8，骨髓中的CD34(+)亚群包括B（CD34(+)CD19(+)）、T/NK（CD34(+)CD7(+)）祖细胞和多能干细胞（CD34(+)Thy1(+)）也不含+8。仅在粒细胞-红细胞-巨噬细胞-巨核细胞集落形成单位（CFU-GEMM；CD34(+)CD33(+)）水平的干细胞中鉴定出+8染色体异常。因此可以得出结论，在MDS背景下受8号染色体三体影响的细胞处于CFU-GEMM水平，而淋巴谱系的细胞未受累。这些结果为MDS的生物学研究提供了新的见解，并表明强化化疗和自体骨髓移植可能成为重要的治疗策略。
