LGALS1 acts as a pro-survival molecule in AML

• Published in: Biochimica et biophysica acta. Molecular cell research 2020-10, Vol.1867 (10), p.118785-118785, Article 118785
• Main Authors: Ruvolo, Peter P., Ma, Huaxian, Ruvolo, Vivian R., Zhang, Xiaorui, Post, Sean M., Andreeff, Michael
• Format: Article
• Language: English
• Subjects: Animals; Bone Marrow - pathology; Cell Line, Tumor; Cell Survival; Galectin 1; Galectin 1 - genetics; Galectin 1 - metabolism; Gene Expression Regulation, Leukemic; Gene Ontology; Humans; Leukemia; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - metabolism; Leukemia, Myeloid, Acute - pathology; Male; Mice, Inbred NOD; Mice, SCID; p53; Prognosis; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Small Interfering - metabolism; RNASeq; Spleen - pathology; THP-1 Cells; Tumor Burden; Tumor Suppressor Protein p53 - metabolism; Xenograft Model Antitumor Assays
• ISSN: 0167-4889; 1879-2596
• DOI: 10.1016/j.bbamcr.2020.118785

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. •LGALS1 suppression in an in vivo AML model prolongs survival of mice.•LGALS1 suppression in an in vivo AML model reduces tumor burden of mice.•LGALS1 suppression alters gene expression and networks affected depend on p53 status.•AML patients with elevated LGALS1 mRNA result in reduced disease free survival.