McGuirk J, Yan Y, Childs B, Fernandez J, Barnett L, Jagiello C, Collins N, O'Reilly R J
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Bone Marrow Transplant. 1998 Aug;22(4):367-74. doi: 10.1038/sj.bmt.1701343.
The development of an in vivo model for the study of CML would be of significant importance in studying its biological behavior and developing novel therapeutic strategies. We examined the ability of human leukemic cells derived from patients in either chronic (CP), accelerated (AP) or blast phase (BP) CML to grow and disseminate in CB17-SCID mice by subcutaneous (s.c.) inoculation without conditioning treatment or administration of cytokines. Additionally, samples derived from patients with CP-CML were injected s.c. into CB17-SCID mice treated with anti-Asialo GM1 (an anti-NK cell antibody) and NOD-SCID mice (absent NK cell activity) to study the potential role of NK cell-mediated anti-leukemic activity in preventing the propagation of CP-CML cells. We observed a significant differential growth pattern of CML cells in the mice such that BP-CML grew rapidly as s.c. tumors and disseminated, while AP-CML or CP-CML cells grew temporarily as small nodules that spontaneously regressed and did not disseminate. This differential growth pattern suggests possible important biological differences. Furthermore, no significant difference in s.c. growth or dissemination of CP-CML samples derived from newly diagnosed patients in untreated CB17-SCID mice and CB-17 SCID mice treated with Anti-Asialo GM1 and NOD-SCID mice occurred, suggesting that factors other than NK cell anti-leukemic activity may be important.
建立用于研究慢性粒细胞白血病(CML)的体内模型对于研究其生物学行为和开发新的治疗策略具有重要意义。我们检测了来自慢性期(CP)、加速期(AP)或急变期(BP)CML患者的人白血病细胞,通过皮下接种在未进行预处理或未给予细胞因子的CB17-SCID小鼠体内生长和播散的能力。此外,将CP-CML患者的样本皮下注射到用抗唾液酸化GM1(一种抗NK细胞抗体)处理的CB17-SCID小鼠和NOD-SCID小鼠(缺乏NK细胞活性)中,以研究NK细胞介导的抗白血病活性在预防CP-CML细胞增殖中的潜在作用。我们观察到小鼠体内CML细胞存在显著的差异生长模式,即BP-CML作为皮下肿瘤迅速生长并播散,而AP-CML或CP-CML细胞暂时生长为小结节,随后自发消退且不播散。这种差异生长模式提示可能存在重要的生物学差异。此外,在未处理的CB17-SCID小鼠、用抗唾液酸化GM1处理的CB-17 SCID小鼠和NOD-SCID小鼠中,新诊断患者的CP-CML样本在皮下生长或播散方面没有显著差异,这表明除NK细胞抗白血病活性外的其他因素可能也很重要。