烷化溶血磷脂选择性杀伤慢性粒细胞白血病骨髓细胞的净化效能

Purging Potential of Alkyl-lysophospholipid in Chronic Myeloid Leukemia Marrow Cell

目的 研究烷化溶血磷脂 (AL P)对慢性粒细胞白血病 (CML )骨髓细胞的杀伤效能及肿瘤坏死因子α(TNF-α)在其中所起的作用。 方法 以甲基纤维素半固体培养液观察 AL P对 CML和健康骨髓祖细胞的作用 ,并用骨髓细胞长期培养 (L TBMC)动态观察 CFU- C的变化。在上述 L TBMC上清液中测定 TNF-α浓度 ,并比较加或不加 TNF-α抗体 CFU- C的变化。 结果 AL P使 CML祖细胞减少但对正常骨髓祖细胞无影响 ,添加 TNF-α抗体能抑制 AL P对 CML骨髓细胞的杀伤作用 ,L TBMC培养 4周后 AL P处理的 CML骨髓祖细胞恢复正常。 结论 AL P选择性杀伤 CML白血病祖细胞 ,此种作用与 TNF-α部分相关 ,AL P处理不影响正常骨髓早期祖细胞自我复制功能 。

Objective\ To study the cytotoxicity of the alkyl\|lysophospholipid ET 18\|OCH3(ALP) on chronic myeloid leukemia(CML) bone marrow and the role of tumor necrosis factor α(TNF\|α) in this cytotoxicity after ALP treatment.\ Methods\ The effect of ALP on normal and CML bone marrow progenitor cells was tested, the dynamic variation of CFU\|C by long term bone marrow culture(LTBMC) with semisolid methylcellulose culture.\ The production of TNF\|α after ALP treatment was measured in the supernatant of LTBMC.\ The LTBMC output of CFU\|C were compared with that adding TNF\|α monoclonal antibody or not adding the antibody.\ Results\ ALP reduced colony growth of CML but did not affect progenitors of normal bone marrow.\ Addition of TNF\|α monoclonal antibody suppressed the cytotoxicity of ALP on CML bone marrow cells.\ All CML bone marrow samples recovered from the ALP treatment after a 4\|week LTBMC culture.\ Conclusion\ The selective suppressive activity of ALP on CML is partly related to TNF\|α and ALP treatment does not affect early progenitors self renewal capacity, which could be considered as a purging approach for CML treatment.\;