The galectin LGALS1 is a glycan binding protein that regulates intracellular (e.g. signal transduction) and extracellular processes (e.g. immunity, leukocyte mobilization) that support cell survival. The protein is best known for its role in RAS signaling. LGALS1 is important in acute lymphoblastic leukemia but its role in acute myeloid leukemia is not well defined. We previously found suppression of LGALS1 in AML cell lines OCI-AML3 and THP-1 sensitized both cell lines to BCL2 inhibitor ABT-737. In this study, we used an in vivo murine OCI-AML3 xenograft model to test whether reduction expression of LGALS1 affects survival. Mice bearing the OCI-AML3 cells with LGALS1 shRNA survived significantly longer than mice with control OCI-AML3 cells. Gene expression profiling using RNASeq was performed using the control and LGALS1 shRNA of p53 WT OCI-AML3 and p53 mutant THP-1 cells. The data reveal distinct differences between the two cell lines in number of genes affected, in pathways associated with these genes, in expression of oncogenes, and in the transcription factors involved. The p53 pathway is prominent in OCI-AML3 cells. An examination of LGALS1 mRNA in an AML patient population reveals elevated LGALS1 mRNA is associated with shorter disease free survival and increased blasts in the BM. This data with the xenograft model data presented suggest LGALS1 may be important in the AML microenvironment. In summary, the data presented here suggest that a strategy targeting LGALS1 may benefit AML patients.

半乳凝素LGALS1是一种聚糖结合蛋白，可调节支持细胞存活的细胞内过程（例如信号转导）和细胞外过程（例如免疫力，白细胞动员）。该蛋白以其在RAS信号传导中的作用而闻名。LGALS1在急性淋巴细胞白血病中很重要，但在急性髓细胞性白血病中的作用尚不明确。我们先前发现在AML细胞系OCI-AML3和THP-1中抑制LGALS1使两种细胞系均对BCL2抑制剂ABT-737敏感。在这项研究中，我们使用了体内小鼠OCI-AML3异种移植模型来测试LGALS1的减少表达是否影响生存。带有LGALS1 shRNA的OCI-AML3细胞的小鼠存活时间明显长于具有对照OCI-AML3细胞的小鼠。使用p53 WT OCI-AML3和p53突变THP-1细胞的对照和LGALS1 shRNA进行使用RNASeq的基因表达谱分析。数据揭示了两种细胞系之间在受影响的基因数量，与这些基因相关的途径，癌基因的表达以及所涉及的转录因子方面的明显差异。p53途径在OCI-AML3细胞中很明显。AML患者人群中LGALS1 mRNA的检查显示，LGALS1 mRNA升高与无病生存期缩短和BM胚泡增多有关。呈现的异种移植模型数据表明LGALS1在AML微环境中可能很重要。总之，此处提供的数据表明，针对LGALS1的策略可能会使AML患者受益。数据揭示了两种细胞系之间在受影响的基因数量，与这些基因相关的途径，癌基因的表达以及所涉及的转录因子方面的明显差异。p53途径在OCI-AML3细胞中很明显。AML患者人群中LGALS1 mRNA的检查显示，LGALS1 mRNA升高与无病生存期缩短和BM胚泡增多有关。呈现的异种移植模型数据表明LGALS1在AML微环境中可能很重要。总之，此处提供的数据表明，针对LGALS1的策略可能会使AML患者受益。数据揭示了两种细胞系之间在受影响的基因数量，与这些基因相关的途径，癌基因的表达以及所涉及的转录因子方面的明显差异。p53途径在OCI-AML3细胞中很明显。AML患者人群中LGALS1 mRNA的检查显示，LGALS1 mRNA升高与无病生存期缩短和BM胚泡增多有关。呈现的异种移植模型数据表明LGALS1在AML微环境中可能很重要。总之，此处提供的数据表明，针对LGALS1的策略可能会使AML患者受益。AML患者人群中LGALS1 mRNA的检查显示，LGALS1 mRNA升高与无病生存期缩短和BM胚泡增多有关。呈现的异种移植模型数据表明LGALS1在AML微环境中可能很重要。总之，此处提供的数据表明，针对LGALS1的策略可能会使AML患者受益。AML患者人群中LGALS1 mRNA的检查显示，LGALS1 mRNA升高与无病生存期缩短和BM胚泡增多有关。呈现的异种移植模型数据表明LGALS1在AML微环境中可能很重要。总之，此处提供的数据表明，针对LGALS1的策略可能会使AML患者受益。