Stanniocalcin 1 is overexpressed in multipotent mesenchymal stromal cells from acute myeloid leukemia patients

Objectives: Multipotent mesenchymal stromal cells (MSC) play a pivotal role in the bone marrow (BM) niche. Stanniocalcin 1 (STC1) secreted by MSC has been demonstrated to promote the survival of neoplastic cells and was suggested a marker for minimal residual disease of acute myeloid leukemia (AML). Therefore, we evaluated the expression of STC1 in MSC from AML patients (MSC_AML) compared to MSC from healthy donors (MSC_HD).Methods: Liquid culture assays of MSC_AML and MSC_HD were performed to compare expansion capacity. Gene expression profiles of MSC_AML vs. MSC_HD were established. Secretion of STC1 was tested by ELISA in MSC_AML vs. MSC_HD and expression of STC1 in AML- vs. HD-BM by immunohistochemistry. In addition, co-cultures of AML cells on MSC were initiated and ultrastructural intercellular communication patterns were investigated. Finally, the effect of blocking STC1 on AML cells was evaluated.Results: MSC_AML showed significant decreased expansion capacity compared to MSC_HD. Gene analysis revealed marked overexpression of STC1 in MSC_AML. ELISA and immunohistochemical findings confirmed this observation. Electron microscopy analysis showed reciprocal stimulation between AML cells and MSC. Blockade of STC1 did not significantly affect AML cell proliferation and apoptosis.Discussion: Characteristics of MSC differ depending on whether they originate from AML patients or from HD. STC1 was mostly overexpressed in MSC_AML compared to MSC_HD. In vitro blockade of STC1, however, was not associated with AML cell proliferation and apoptosis.Conclusion: Differences in expression levels of glycoproteins from MSC_AML compared to MSC_HD not necessarily assume that these molecules are niche-relevant in leukemic disease.