Galectin-9 and PSMB8 overexpression predict unfavorable prognosis in patients with AML

Abstract

Acute myeloid leukemia (AML) is a deadly heterogeneous hematologic malignancy. Despite the well-characterized genetic characteristics and new promising targeted therapies for AML, the clinical outcome remains suboptimal. Galectin-9 (Gal-9) is a good potential target due to its immunosuppressive capacity in inflammatory processes. In our study, we firstly performed a wide range of integrated bioinformatical approach to assess the importance of Gal-9 by analyzing the expression, potential function and prognostic impact in AML. The results indicated that Gal-9 is overexpressed in AML cells, especially when relapse after hematopoietic stem cell transplantation (HSCT) and predicts poor prognosis. Co-expression analysis showed Gal-9 has a strong positive correlation with proteasome subunit beta type-8 (PSMB8), which was also highly expressed in AML with poor prognosis, implying a synergy in cell survival, cell signaling and the development of AML. In summary, we have confirmed the overexpression of Gal-9 and its partner PSMB8 in AML and validated their importance as prognostic factors. We propose that Gal-9 and PSMB8 could be a promising molecular target for treatment of AML and may provide more combined treatment options, especially in patients with relapse after HSCT.

Development and characterization of anti-galectin-9 antibodies that protect T cells from galectin-9-induced cell death

“…As such, the correlation between Gal-9 expression and patient prognosis also varies across cancer types. Although high Gal-9 expression is associated with unfavorable prognosis in some hard-to-treat cancers, such as brain tumor ( 34 ), pancreatic cancer ( 16 , 35 ), and acute myeloid leukemia ( 36 ), it is associated with favorable outcome in some other cancers ( 13 ). In the latter cases, Gal-9 expression likely indicates the activated status of immune responses, as Gal-9 is mainly expressed by immune cells including T cells and induced in tumor cells by inflammatory cytokines such as interferons ( 6 , 37 ).…”

SASH3 is an unfavorable prognostic immune biomarker in patients with acute myeloid leukemia(AML).

“…Our study evaluated the co-expression of SASH3 genes in AML from the UALCAN (http://ualcan.path.uab.edu/) and GEPIA (http://gepia.uab.edu/) databases [23]. Using a web tool (http://bioinformatics.psb.ugent.be/webtools/Venn/), the top 500 genes most closely co-expressed with SASH3 genes were extracted from each of the two databases, and the nal 380 common co-expressed genes were obtained by taking intersections.…”

A new emerging target in cancer immunotherapy: Galectin-9 (LGALS9)

“…Gal-9 is overexpressed in AML, especially when relapse after hematopoietic stem cell transplantation (HSCT), suggesting a poor prognosis. There is a strong positive correlation between Gal-9 and proteasome subunit beta type-8 (PSMB8), which plays a synergistic role in the progression of AML 99 . Drug resistance is a real barrier to chemotherapy in patients with many cancers, including AML, and has multiple forms, namely, multidrug resistance (MDR).…”