Tasquinimod Improves Erythropoiesis and Mitigates Bone Loss in Myelodysplastic Mice

Myelodysplastic neoplasms (MDS) are characterized by ineffective hematopoiesis, peripheral cytopenia, and a risk of transforming into acute myeloid leukemia (AML). Interestingly, MDS is also associated with an increased prevalence of osteoporosis. Studies have suggested that dysregulated innate immune responses and a proinflammatory bone marrow (BM) microenvironment play significant roles in the pathogenesis of MDS. Targeting inflammatory pathways, especially in low-risk MDS patients, presents a potential strategy to modulate the progression of the disease. One such candidate is Tasquinimod (TASQ, ABR-215050, Active Biotech AB), a small-molecule oral inhibitor and second-generation quinoline-3-carboxamide compound. TASQ binds to the inflammatory protein S100A9 and inhibits its interaction with the proinflammatory toll-like receptor 4, thereby displaying both immunomodulatory and antitumor properties. Our in vitrodata provided evidence for a rescuing effect of TASQ on inflammatory signal-primed MDS stromal cells, leading to enhanced hematopoietic support.