van Bekkum D W, Prins M E, Hagenbeek A
Blood Cells. 1981;7(1):91-103.
One characteristic feature of human acute leukaemia is a depression of normal haemopoiesis which, according to the results of in vitro colony formation, seems to be more severe in acute myeloid leukaemia (AML) than in acute lymphocytic leukaemia (ALL). In our rat model for AML, the transplantable Brown Norway myeloid leukaemia (BNML), near total suppression of haemopoiesis was observed in a relatively early stage of the disease because of the physical disappearance of haemopoietic stem cells (HSC) from the bone marrow, which was only partly compensated by an increased number of HSC in the spleen. The few HSC remaining in the BNML bone marrow in the terminal stage of the disease were mostly out of cycle, in contrast to the HSC in normal rat marrow. Studies with injected labelled leukaemic cells revealed that both BNML and cells of a transplantable lymphatic leukaemia home in the subendosteal region of the femoral bone marrow. Subsequently, ALL cells become randomly distributed over the whole marrow space, while BNML cells remain localized in the subendosteal region. The latter area contains in normal rat marrow a higher proportion of proliferating blast cells than the central area of the marrow, which is reminiscent of the kinetic gradient described in mouse bone marrow by Shackney et al. [22]. These observations support the hypothesis that the depression of normal haemopoiesis in AML is caused by a specific localization and proliferation of AML cells in the subendosteal area, which normally provides the optimal microenvironment for HSC self-replication. In ALL the more severe depression of haemopoiesis occurs in a later stage and is caused by random replacement of HSC as a result of non-specific overgrowth.
人类急性白血病的一个特征是正常造血功能受到抑制。根据体外集落形成的结果，急性髓系白血病（AML）中这种抑制似乎比急性淋巴细胞白血病（ALL）更严重。在我们的AML大鼠模型——可移植的棕色挪威髓系白血病（BNML）中，在疾病相对早期就观察到造血功能几乎完全受到抑制，这是因为造血干细胞（HSC）从骨髓中物理性消失，而脾脏中HSC数量的增加只能部分补偿这种消失。与正常大鼠骨髓中的HSC相比，疾病终末期BNML骨髓中残留的少数HSC大多处于非增殖周期。对注射标记白血病细胞的研究表明，BNML和一种可移植淋巴白血病的细胞都归巢于股骨骨髓的骨内膜下区域。随后，ALL细胞随机分布于整个骨髓空间，而BNML细胞仍局限于骨内膜下区域。在正常大鼠骨髓中，该区域增殖的原始细胞比例高于骨髓中央区域，这让人联想到Shackney等人[22]在小鼠骨髓中描述的动力学梯度。这些观察结果支持了这样一种假说，即AML中正常造血功能的抑制是由AML细胞在骨内膜下区域的特定定位和增殖引起的，该区域通常为HSC自我复制提供最佳微环境。在ALL中，更严重的造血抑制发生在疾病后期，是由非特异性过度生长导致HSC被随机替代所致。
