Nardi Valentina, Naveiras Olaia, Azam Mohammad, Daley George Q
Division of Hematology/Oncology, Children's Hospital Boston, MA 02115, USA.
Blood. 2009 Apr 16;113(16):3813-20. doi: 10.1182/blood-2008-07-167189. Epub 2009 Jan 26.
Interferon (IFN) is effective at inducing complete remissions in patients with chronic myelogenous leukemia (CML), and evidence supports an immune mechanism. Here we show that the type I IFNs (alpha and beta) regulate expression of the IFN consensus sequence-binding protein (ICSBP) in BCR-ABL-transformed cells and as shown previously for ICSBP, induce a vaccine-like immunoprotective effect in a murine model of BCR-ABL-induced leukemia. We identify the chemokines CCL6 and CCL9 as genes prominently induced by the type I IFNs and ICSBP, and demonstrate that these immunomodulators are required for the immunoprotective effect of ICSBP expression. Insights into the role of these chemokines in the antileukemic response of IFNs suggest new strategies for immunotherapy of CML.
干扰素(IFN)在诱导慢性粒细胞白血病(CML)患者完全缓解方面有效,且有证据支持其免疫机制。在此我们表明,I型干扰素(α和β)调节BCR-ABL转化细胞中干扰素共有序列结合蛋白(ICSBP)的表达,并且如先前对ICSBP的研究所示,在BCR-ABL诱导的白血病小鼠模型中诱导出类似疫苗的免疫保护作用。我们鉴定出趋化因子CCL6和CCL9是由I型干扰素和ICSBP显著诱导的基因,并证明这些免疫调节剂是ICSBP表达产生免疫保护作用所必需的。对这些趋化因子在干扰素抗白血病反应中作用的深入了解为CML的免疫治疗提出了新策略。