Dendritic Cells in Myelodysplastic Syndromes

From Pathogenesis to Immunotherapy

Nathalie Kerkhoff; Hetty J Bontkes; Theresia M Westers; Tanja D de Gruijl; Shahram Kordasti; Arjan A van de Loosdrecht


Immunotherapy. 2013;5(6):621-637. 

In This Article

Abstract and Introduction


Myelodysplastic syndromes (MDS) are clonal disorders of the hematopoietic stem cell characterized by ineffective hematopoiesis leading to peripheral cytopenias. Different processes are involved in its pathogenesis, such as (epi)genetic alterations and immunological dysfunctions. The nature of immune dysregulation is markedly different between various MDS risk groups. In low-risk MDS, the immune system is in a proinflammatory state, whereas in high-risk disease, immunosuppressive features facilitate expansion of the dysplastic clone and can eventually lead to disease progression to acute myeloid leukemia. Various cell types contribute to dysregulation of immune responses in MDS. Dendritic cells (DCs) are important regulators of immunity. However, the role of DCs in MDS has yet to be elucidated. It has been suggested that impaired DC function can hamper adequate immune responses. This review focuses on the involvement of DCs in immune dysregulation in low- and high-risk MDS and the implications for DC-targeted therapies.


Myelodysplastic syndromes (MDS) constitute a group of heterogeneous clonal hematopoietic stem cell disorders with a propensity to evolve into acute myeloid leukemia (AML). Different prognostic scoring systems are currently used to predict the overall survival of patients with MDS and the risk of transformation toward AML.[1–3] The underlying pathogenesis of MDS is still poorly understood. It is believed that a multistep process results in the development of the disease. One of the factors that contributes to this process includes genetic alterations, which lead to the activation or inactivation of oncogenes and tumor suppressor genes, respectively. Epigenetic changes, such as DNA methylation and histone acetylation, might also play a role.[4] Gene transcription dysregulation can result in genomic instability in MDS.[5,6]

Another aspect of MDS pathogenesis is immune dysregulation. This hypothesis is supported by the presence of autoimmune disorders in MDS patients,[7–9] the improvement of hematopoiesis following treatment with immunosuppressive therapies, such as antithymocyte globulin[10] and cyclosporine in low-risk MDS,[11] and the dysfunction of several immune system compartments.[12–18] It is believed that the nature of this immune dysfunction is markedly different between various MDS risk groups. In low-risk MDS, the immune system is in an activated, proinflammatory state, which leads to a high apoptosis rate of hematopoietic progenitors, whereas in high-risk disease, an immunosuppressive environment enables the dysplastic clone to expand and evade immunosurveillance (Table 1). However, the exact mechanisms of action and the extent to which different cells are involved still need to be elucidated. This article reviews the general role of dendritic cells (DCs) and their possible contribution to immune dysregulation in low- and high-risk MDS in particular. Furthermore, their potential as a target for immunotherapeutic regimens in MDS will be discussed.