Francis G E, Berney J J, Wing M A, Tuma G A, Hoffbrand A V
Leuk Res. 1982;6(2):165-73. doi: 10.1016/0145-2126(82)90022-4.
The purpose of this study was to determine possible mechanisms for the recently observed association between insensitivity of acute myeloid leukemia (AML) clonogenic cells to colony stimulating activity (CSA) and poor response to induction chemotherapy. The bone marrow endogenous CSA was determined using semi-solid agar cultures by measuring the response of the AML patients' own clonogenic cells to endogenous CSA. The results show that whereas 31% (5/16) of patients at presentation have deficient bone marrow endogenous CSA production, over 50% (11/21) have relative deficiency of endogenous CSA, due to insensitivity of the patients' clonogenic cells to CSA. Although there is an association between relative deficiency of endogenous CSA and a poor response to therapy, the relationship is not close enough to explain the previously observed highly significant correlation between insensitivity to CSA and poor response to therapy. The CSA-insensitive phenotype and poor response to therapy, one via the tendency to relative endogenous CSA deficiency in the CSA-insensitive group and another via some additional feature of these poor response AML phenotypes which is independent of the presence or absence of endogenous CSA deficiency.
本研究的目的是确定近期观察到的急性髓系白血病(AML)克隆形成细胞对集落刺激活性(CSA)不敏感与诱导化疗反应不佳之间关联的可能机制。通过测量AML患者自身克隆形成细胞对内源性CSA的反应,采用半固体琼脂培养法测定骨髓内源性CSA。结果显示,初诊时31%(5/16)的患者骨髓内源性CSA产生不足,超过50%(11/21)的患者存在内源性CSA相对不足,原因是患者的克隆形成细胞对CSA不敏感。虽然内源性CSA相对不足与治疗反应不佳之间存在关联,但这种关系不够紧密,无法解释先前观察到的对CSA不敏感与治疗反应不佳之间高度显著的相关性。CSA不敏感表型与治疗反应不佳,一种是通过CSA不敏感组中内源性CSA相对不足的倾向,另一种是通过这些治疗反应不佳的AML表型的一些额外特征,这些特征与内源性CSA不足的存在与否无关。