Department of Cell Biology and Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Cancer Cell. 2012 Aug 14;22(2):194-208. doi: 10.1016/j.ccr.2012.06.027.
Homeobox domain-containing transcription factors are important regulators of hematopoiesis. Here, we report that increased levels of nonclustered H2.0-like homeobox (HLX) lead to loss of functional hematopoietic stem cells and formation of aberrant progenitors with unlimited serial clonogenicity and blocked differentiation. Inhibition of HLX reduces proliferation and clonogenicity of leukemia cells, overcomes the differentiation block, and leads to prolonged survival. HLX regulates a transcriptional program, including PAK1 and BTG1, that controls cellular differentiation and proliferation. HLX is overexpressed in 87% of patients with acute myeloid leukemia (AML) and independently correlates with inferior overall survival (n = 601, p = 2.3 × 10(-6)). Our study identifies HLX as a key regulator in immature hematopoietic and leukemia cells and as a prognostic marker and therapeutic target in AML.
同源盒结构域转录因子是造血的重要调节因子。在这里，我们报告说，非簇集 H2.0 样同源盒 (HLX) 水平的增加导致功能性造血干细胞的丧失，并形成具有无限系列克隆性和分化阻断的异常祖细胞。HLX 的抑制可降低白血病细胞的增殖和克隆形成能力，克服分化阻断，并导致存活时间延长。HLX 调节包括 PAK1 和 BTG1 在内的转录程序，控制细胞分化和增殖。87%的急性髓系白血病 (AML) 患者存在 HLX 过表达，与总体生存不良独立相关（n=601，p=2.3×10(-6))。我们的研究将 HLX 鉴定为不成熟造血细胞和白血病细胞中的关键调节因子，以及 AML 的预后标志物和治疗靶点。
