Table 2 Currently available therapeutic options for patients with MDS and their potential impact on the functional properties of the osteo-hematopoietic niche

HMA (azacitidine/decitabine)

*Demethylation of Wnt-antagonist gene promoters and reduction of the non-phosphorylated β-catenin in HSPCs¹⁰⁵

*Upregulation of BMP-2, -4 and -6 expression in osteoblasts¹⁰⁶

Lenalidomide

*Inhibiting angiogenesis, suppressing the production of proinflammatory cytokines (for example, TNFα), inhibiting cytokinesis in MDS cell lines⁷⁸

*Decrease of CXCL12 secretion by MSPCs, thereby detaching HSPC from their niche; enhancement of CD29 (integrin β1) expression⁶⁹

*Increase in expression of adhesion molecules in HSPCs; increase in CXCL12 and ICAM-1 secretion by MSPCs, thus improving their hematopoiesis-supporting capacity⁷²

ACE-011/ACE-536

*Trap of important soluble factors (that is, activin, BMP-2, BMP-6) secreted by stromal cells^{107, 112}

*Modulating of the SMAD signaling pathway, which leads to changes in the transcription of SMAD-regulated target genes¹¹³

Iron chelation

*Activation of Wnt/β-catenin pathway and induction of osteoblastic differentiation of MSPCs¹¹⁷