The inflammatory microenvironment in MDS

Abstract

Myelodysplastic syndromes (MDS) are a collection of pre-malignancies characterized by impaired proliferation and differentiation of hematopoietic stem cells and a tendency to evolve into leukemia. Among MDS's pathogenic mechanisms are genetic, epigenetic, apoptotic, differentiation, and cytokine milieu abnormalities. Inflammatory changes are a prominent morphologic feature in some cases, with increased populations of plasma cells, mast cells, and lymphocytes in bone marrow aspirates. Accumulating evidence suggests that the bone marrow microenvironment contributes to MDS disease pathology, with microenvironment alterations and abnormality preceding, and facilitating clonal evolution in MDS patients. In this review, we focus on the inflammatory changes involved in the pathology of MDS, with an emphasis on immune dysfunction, stromal microenvironment, and cytokine imbalance in the microenvironment as well as activation of innate immune signaling in MDS patients. A better understanding of the mechanism of MDS pathophysiology will be beneficial to the development of molecular-targeted therapies in the future.

Fig. 1

Inflammatory bone marrow microenvironment-induced Model of MDS Pathogenesis in the Elderly. Aging, along with chronic inflammation stimulation leads to MDSC accumulation and activation (1, 2). Inflammatory cytokines and soluble factors, such as ROS and S100A9 (3), cause increased apoptosis of uncommitted HSPCs (4) as well as genomic instability (5). Age-dependent development of MDS via hematopoietic driver somatic mutations leads to the accumulation of hematopoietic clones, including selection of malignant clones (6)