División de Inmunología, Centro de Investigación Biomédica de Occidente - IMSS, Sierra Mojada No. 800, CP 44340, Guadalajara, Jalisco, Mexico.
J Exp Clin Cancer Res. 2011 Dec 20;30(1):112. doi: 10.1186/1756-9966-30-112.
The Three-amino acid-loop-extension (TALE) superfamily of homeodomain-containing transcription factors have been implicated in normal hematopoiesis and in leukemogenesis and are important survival, differentiation, and apoptosis pathway modulators. In this work, we determined the expression levels of TALE genes in leukemic-derived cell lines, in blood samples of patients with Acute lymphoblastic leukemia (ALL), and in the blood samples of healthy donors.
Here we show increased expression of MEIS1, MEIS2, and PREP1 genes in leukemia-derived cell lines compared with blood normal cells. High levels of MEIS1 and PREP1, and low levels of PBX4 expression were also founded in samples of patients with ALL. Importantly, silencing of MEIS1 decreases the proliferation of leukemia-derived cells but increases their survival after etoposide treatment. Etoposide-induced apoptosis induces down-regulation of MEIS1 expression or PREP1 up-regulation in chemotherapy-resistant cells.
Our results indicate that up-regulation of MEIS1 is important for sustaining proliferation of leukemic cells and that down-regulation of MEIS1 or up-regulation of PREP1 and PBX genes could be implicated in the modulation of the cellular response to chemotherapeutic-induced apoptosis.
三氨基酸环延伸（TALE）超家族的同源域转录因子在家系造血和白血病发生中起重要作用，是重要的生存、分化和凋亡途径调节剂。在这项工作中，我们测定了 TALE 基因在白血病衍生细胞系、急性淋巴细胞白血病（ALL）患者的血液样本和健康供者的血液样本中的表达水平。
我们发现与正常血细胞相比，白血病衍生细胞系中 MEIS1、MEIS2 和 PREP1 基因表达上调。在 ALL 患者的样本中还发现 MEIS1 和 PREP1 水平高，PBX4 表达水平低。重要的是，沉默 MEIS1 可降低白血病衍生细胞的增殖，但增加依托泊苷处理后的存活。依托泊苷诱导的凋亡诱导化疗耐药细胞中 MEIS1 表达下调或 PREP1 上调。
我们的结果表明 MEIS1 的上调对维持白血病细胞的增殖很重要，而 MEIS1 的下调或 PREP1 和 PBX 基因的上调可能与化疗诱导的细胞凋亡反应的调节有关。
