Ghanta V K, Hiramoto R N, Davis D W, Hiramoto N S
Cancer Res. 1980 Jul;40(7):2372-6.
MOPC 104E myeloma cells are brought under host regulation after treatment with cyclophosphamide, 1,3-bis(2-chloroethyl)-1-nitrosourea, or cis-dichlorodiammineplatinum(II). The first indication of this phenomenon is the plateau level of immunoglobulin M(lambda) [IgM(lambda)]. The myeloma recurs more frequently in animals with high plateau levels of IgM(lambda) even when remission is maintained for greater than 200 days. The growth rate of the recurring tumor is altered when compared with the original tumor in the same individual. Different drugs and dosages produce stable myeloma of different sizes. Treatment with cyclophosphamide (10 to 200 mg/kg), or 1,3-bis(2-chloroethyl)-1-nitrosourea (25 mg/kg) gives stable myeloma that produces low plateau levels of IgM(lambda). This myeloma does not show late recurrence. Combination of 1,3-bis(2-chloroethyl)-1-nitrosourea, cyclophosphamide, and cis-dichlorodiammineplatinum(II) in low doses or cis-dichlorodiammineplatinum(II) alone gives a stable myeloma clone(s) which produces IgM(lambda) which plateaus at higher levels, and the myeloma clone recurs relatively late in the life of the animal. These results show that treatment does not lead to the elimination of the dominant myeloma clone. Clonal dominance is, however, broken when the proliferative potential is interrupted by drug treatment. The resulting long stable phase supports the view that the proliferation, the expression of the plasma cell maturation sequences, and the secretion of IgM(lambda) are under normal host regulation. Aging presumably causes a loss of regulatory control permitting clonal expansion and recurrence of the myeloma in animals with high plateau levels of the IgM(lambda). The MOPC 104E myeloma model demonstrates for the first time a conversion of the malignant form to the indolent form as seen for humans.
用环磷酰胺、1,3 - 双（2 - 氯乙基）- 1 - 亚硝基脲或顺 - 二氯二氨合铂（II）处理后，MOPC 104E骨髓瘤细胞受到宿主调节。这种现象的首个迹象是免疫球蛋白M（λ）[IgM（λ）]的平台期水平。即使缓解期维持超过200天，IgM（λ）平台期水平高的动物中骨髓瘤复发更频繁。与同一个体的原发肿瘤相比，复发肿瘤的生长速率发生改变。不同药物和剂量产生不同大小的稳定骨髓瘤。用环磷酰胺（10至200mg/kg）或1,3 - 双（2 - 氯乙基）- 1 - 亚硝基脲（25mg/kg）治疗可产生稳定的骨髓瘤，其产生低水平的IgM（λ）平台期。这种骨髓瘤不会出现晚期复发。低剂量的1,3 - 双（2 - 氯乙基）- 1 - 亚硝基脲、环磷酰胺和顺 - 二氯二氨合铂（II）联合使用或单独使用顺 - 二氯二氨合铂（II）可产生稳定的骨髓瘤克隆，其产生的IgM（λ）在较高水平达到平台期，且骨髓瘤克隆在动物生命后期相对较晚复发。这些结果表明治疗不会导致优势骨髓瘤克隆的消除。然而，当药物治疗中断增殖潜能时，克隆优势被打破。由此产生的长期稳定期支持这样一种观点，即增殖、浆细胞成熟序列的表达以及IgM（λ）的分泌受正常宿主调节。衰老可能导致调节控制丧失，从而允许IgM（λ）平台期水平高的动物中骨髓瘤克隆扩增和复发。MOPC 104E骨髓瘤模型首次证明了恶性形式向惰性形式的转变，就像在人类中看到的那样。
