Pierson B A, Miller J S
Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, USA.
Leuk Lymphoma. 1997 Nov;27(5-6):387-99. doi: 10.3109/10428199709058306.
Chronic myelogenous leukemia (CML) is a lethal disease of the hematopoietic stem cell. Bone marrow transplantation has highlighted the importance of allogeneic disparity in maintaining remissions in CML. However, it has been unclear whether the immune effect against CML is mediated by T cells, natural killer cells (NK) or a combination of both. We have previously demonstrated that autologous activated NK are capable of selectively lysing malignant CML progenitors while sparing benign progenitors. NK effectors may play an important role in CML since NK lytic function, clonogenic frequency and proliferative capacity decrease as CML progresses from chronic phase to advanced phase and blast crisis. Incubation of CML NK with IL-2 is capable of restoring cytolytic activity to normal levels. We hypothesize that activated NK represent a potential therapy against CML to maintain remissions in a minimal residual disease setting induced by autologous transplantation. Clinical trials are in progress to test whether IL-2 based immunotherapy and activated cell infusions play a therapeutic role in CML.
慢性粒细胞白血病（CML）是一种造血干细胞的致命疾病。骨髓移植凸显了同种异体差异在维持CML缓解中的重要性。然而，针对CML的免疫效应是由T细胞、自然杀伤细胞（NK）介导还是两者共同介导尚不清楚。我们之前已经证明，自体活化的NK能够选择性地裂解恶性CML祖细胞，同时保留良性祖细胞。NK效应细胞可能在CML中发挥重要作用，因为随着CML从慢性期发展到进展期和急变期，NK的裂解功能、克隆形成频率和增殖能力会下降。用白细胞介素-2孵育CML患者的NK能够将细胞溶解活性恢复到正常水平。我们假设活化的NK代表了一种针对CML的潜在疗法，可在自体移植诱导的微小残留病环境中维持缓解。目前正在进行临床试验，以测试基于白细胞介素-2的免疫疗法和活化细胞输注在CML中是否发挥治疗作用。
