Expression of WNT Family Genes in Mesenchymal Stromal Cells of the Hematopoietic Niche in Patients with Different Responses to Multiple Myeloma Treatment

TL;DR

This study explores how WNT genes in bone marrow cells relate to treatment outcomes in multiple myeloma patients.

Contribution

The study identifies WNT3A, WNT5A, WNT10B, and β-catenin as potential markers for predicting treatment response in multiple myeloma.

Findings

WNT3A, WNT5A, WNT10B, and β-catenin levels in bone marrow differ based on treatment response.

WNT3A is mainly in mesenchymal stromal cells, while WNT5A and WNT10B are in plasma cells.

WNT genes and CTNNB1 show differential expression in mesenchymal stromal cells from patients versus healthy donors.

Abstract

Mesenchymal stromal cells of the tumor microenvironment (TME) play a significant role in the progression of multiple myeloma (MM). The cells of the TME demonstrate resistance to treatment, thereby creating a favorable environment for disease relapse. The status of the TME during remission is poorly understood. An association between treatment response and TME status (including signaling pathways) has been suggested. One of the key players in the establishment of the MM TME is WNT signaling. In this study, we evaluated the expression of WNT family proteins in the TME and MM cells to assess their potential as TME markers and predictors of treatment response. A bioinformatic analysis of normal and malignant plasma cells, combined with an analysis of published data, revealed the following differentially expressed WNT genes: WNT5A, WNT10B, CTNNB1, and WNT3A. Immunohistochemical staining with the antibodies against the proteins encoded by the genes was conducted on trephine biopsy samples of bone marrow from healthy donors and patients with different responses to therapy. A quantitative analysis of the immunohistochemical data revealed differences in the amounts of WNT3A, WNT5A, WNT10B, and β-catenin proteins in the bone marrow before treatment depending on the subsequent responses of the patients to therapy. Multiplex fluorescent immunohistochemical staining with tyramide signal amplification revealed that WNT3A was predominantly present in mesenchymal stromal cells, whereas WNT5A and WNT10B were primarily observed in plasma cells. β-catenin was detected in both cell types. We analyzed the mRNA levels of the WNT gene family and CTNNB1 in MSC cultures from healthy donors and patients using qPCR. These genes were differentially expressed in MSC cultures derived from patients and healthy donors, as well as between patients grouped according to their response to therapy. Therefore, WNT proteins and β-catenin can be considered potential markers to assess the state of the tumor niche.

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