Metcalf D, Rasko J E
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Leukemia. 1993 Jun;7(6):878-86.
Injection of 10(6) immortalized, but non-leukemic, granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent FDC-P1 cells into GM-CSF transgenic hybrid mice with elevated GM-CSF levels led to death within three months with elevated blast cell numbers in the blood, massive organ infiltration by blast cells, and associated anemia and thrombocytopenia. No disease developed within this period in littermate mice injected with 10(6) FDC-P1 cells. All moribund transgenic recipients contained transformed FDC-P1 cells able to produce rapidly-growing transplanted leukemias in syngeneic normal DBA/2 recipients. The leukemias appeared to arise in the primary recipients by independent transformation events. The transformed cells from different mice differed in their in vitro growth characteristics, their ability to produce GM-CSF or multipotential CSF, and in the nature of the transplanted tumors derived from the primary cells. While all primary recipients at death contained fully transformed leukemic cells, the bulk of the large population of FDC-P1 cells appeared either to be untransformed or to have altered characteristics not yet representing full transformation. If the FDC-P1 engrafted model has some validity for myelodysplasia, the results suggest that sustained CSF administration to myelodysplastic patients possessing abnormal, potentially preleukemic, granulocyte-macrophage populations may increase the risk of death either from accumulated pretransformed or from fully transformed leukemic cells.
将10(6)个永生化但非白血病的、依赖粒细胞-巨噬细胞集落刺激因子（GM-CSF）的FDC-P1细胞注射到GM-CSF水平升高的GM-CSF转基因杂交小鼠体内，导致小鼠在三个月内死亡，血液中原始细胞数量增加，原始细胞大量浸润器官，并伴有贫血和血小板减少。注射10(6)个FDC-P1细胞的同窝小鼠在此期间未发病。所有濒死的转基因受体均含有能够在同基因正常DBA/2受体中产生快速生长的移植性白血病的转化FDC-P1细胞。白血病似乎是在原发性受体中通过独立的转化事件产生的。来自不同小鼠的转化细胞在体外生长特性、产生GM-CSF或多能CSF的能力以及源自原代细胞的移植肿瘤的性质方面存在差异。虽然所有死亡的原发性受体都含有完全转化的白血病细胞，但大量的FDC-P1细胞群体似乎要么未转化，要么具有尚未代表完全转化的改变特征。如果FDC-P1植入模型对骨髓发育异常有一定的有效性，结果表明，持续向具有异常的、潜在白血病前期的粒细胞-巨噬细胞群体的骨髓发育异常患者施用CSF，可能会增加因累积的预转化细胞或完全转化的白血病细胞而导致死亡的风险。
