Sparrow R L, O'Flaherty E, Blanksby T M, Szer J, Van Der Weyden M B
Clinical Haematology and Bone Marrow Transplantation Research Unit, Alfred Hospital, Prahran, Victoria, Australia.
Leuk Res. 1997 Jan;21(1):29-36. doi: 10.1016/s0145-2126(96)00068-9.
The ability of bone marrow (BM) stroma derived from patients with acute myeloid leukemia (AML) or chronic myeloid leukemia (CML) to support normal hematopoiesis was investigated using a two-stage long-term bone marrow culture (LTBMC) procedure. Of particular interest was whether leukemia-derived stroma were capable of supporting the very immature, uncommitted hematopoietic progenitor cells (HPC) which are considered to have a higher dependence and association with the BM stroma than the more mature committed HPC. Confluent stromal layers were recharged with selected populations of normal HPC enriched for the CD34+CD38- cells (immature, uncommitted HPC) or the CD34+CD38+ cells (mature, committed HPC). The weekly output of clonable granulocyte-macrophage progenitor cells (CFU-GM) was used as an indicator of the hematopoietic-supporting ability of the cultures. Stromal layers derived from 5/7 patients newly diagnosed with AML, showed significantly depressed ability to support the CD34+CD38- cells compared to stroma derived from normal donors. The supporting function of the AML-derived stroma for the more mature CD34+CD38+ cells was similar to that of the normal stroma (3/3 cases). Stromal layers derived from patients with chronic-phase CML showed normal or enhanced supporting function for the CD34+CD38- cells (5/6 cases), and likewise for the CD34+CD38+ cells (3/3 cases). This study revealed a selective defect in the ability of BM stroma from patients with AML to support the maturation of normal early uncommitted HPC, represented by the CD34+CD38- cells, whilst the ability to support the committed CD34+CD38+ cells was not affected. This suggests that the BM microenvironment may be implicated in the disease mechanism of AML. It does not, however, appear to be as clearly implicated in chronic-phase CML.
采用两阶段长期骨髓培养（LTBMC）程序，研究了急性髓系白血病（AML）或慢性髓系白血病（CML）患者来源的骨髓（BM）基质支持正常造血的能力。特别令人感兴趣的是，白血病来源的基质是否能够支持非常不成熟、未定向的造血祖细胞（HPC），这些细胞被认为比更成熟的定向HPC对BM基质有更高的依赖性和关联性。将汇合的基质层用富集了CD34+CD38-细胞（不成熟、未定向HPC）或CD34+CD38+细胞（成熟、定向HPC）的正常HPC选定群体重新接种。每周可克隆的粒细胞-巨噬细胞祖细胞（CFU-GM）产量用作培养物造血支持能力的指标。与正常供体来源的基质相比，7例新诊断为AML的患者中有5例来源的基质层对CD34+CD38-细胞的支持能力明显降低。AML来源的基质对更成熟的CD34+CD38+细胞的支持功能与正常基质相似（3/3例）。慢性期CML患者来源的基质层对CD34+CD38-细胞显示正常或增强的支持功能（5/6例），对CD34+CD38+细胞同样如此（3/3例）。这项研究揭示了AML患者BM基质支持以CD34+CD38-细胞为代表的正常早期未定向HPC成熟的能力存在选择性缺陷，而支持定向CD34+CD38+细胞的能力未受影响。这表明BM微环境可能与AML的发病机制有关。然而，它似乎与慢性期CML的关系不那么明显。
