a Department of Pediatric Hematology/Oncology and of Cell and Gene Therapy , Bambino Gesù Children's Hospital, IRCCS , Rome , Italy.
b SAFU, Department of Research , Advanced Diagnostics, and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute , Rome , Italy.
Cell Cycle. 2018;17(11):1286-1290. doi: 10.1080/15384101.2018.1480227. Epub 2018 Jul 25.
B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common malignancy in childhood. Despite the high cure-rate, identifying new druggable molecular targets is still of great interest. In a cohort of BCP-ALL pediatric patients, irrespectively of the molecule/karyotype lesions found, we recently observed high expression of c-Myc and Che-1/AATF, which disappears at time of remission. Study of the molecular mechanisms involved in this co-expression revealed that Che-1 expression was crucial for induction of blast-cell proliferation driven by c-Myc. Furthermore, Che-1/AATF silencing in primary BCP-ALL cell lines improves responsiveness to chemotherapy. These data individuate Che-1 as a possible novel target in the treatment of BCP-ALL able to affect c-Myc-driven tumorigenicity.
B 细胞前体急性淋巴细胞白血病(BCP-ALL)是儿童期最常见的恶性肿瘤。尽管治愈率很高,但寻找新的可用药理学分子靶点仍然具有重要意义。在一组 BCP-ALL 儿科患者中,无论发现何种分子/核型病变,我们最近观察到 c-Myc 和 Che-1/AATF 的高表达,这些表达在缓解时消失。对涉及这种共表达的分子机制的研究表明,Che-1 的表达对于由 c-Myc 驱动的母细胞增殖的诱导至关重要。此外,原发性 BCP-ALL 细胞系中 Che-1/AATF 的沉默可提高对化疗的反应性。这些数据表明 Che-1 可能是一种新的治疗 BCP-ALL 的靶点,能够影响 c-Myc 驱动的肿瘤发生。