Diagnosis of Myelodysplastic Syndromes: From Immunological Observations to Clinical Applications

Abstract

Myelodysplastic syndromes (MDS) constitute a very heterogeneous group of diseases with a high prevalence in elderly patients and a propensity for progression to acute myeloid leukemia. The complexity of these hematopoietic malignancies is revealed by the multiple recurrent somatic mutations involved in MDS pathogenesis and the paradoxical common phenotype observed in these patients characterized by ineffective hematopoiesis and cytopenia. In the context of population aging, the incidence of MDS will strongly increase in the future. Thus, precise diagnosis and evaluation of the progression risk of these diseases are imperative to adapt the treatment. Dysregulations of both innate and adaptive immune systems are frequently detected in MDS patients, and their critical role in MDS pathogenesis is now commonly accepted. However, different immune dysregulations and/or dysfunctions can be dynamically observed during the course of the disease. Monitoring the immune system therefore represents a new attractive tool for a more precise characterization of MDS at diagnosis and for identifying patients who may benefit from immunotherapy. We review here the current knowledge of the critical role of immune dysfunctions in both MDS and MDS precursor conditions and discuss the opportunities offered by the detection of these dysregulations for patient stratification.

Myelodysplastic Neoplasms: The Impact of Clonality on Inflammatory-Degenerative Diseases of the Elderly

“…59 In MDS, key drivers of tumorigenesis are related to aberrant innate immune activation and proinflammatory signaling interacting within the malignant clone and the BM microenvironment. 60 Aging, chronic infection and autoimmune/autoinflammatory disease are all factors that promote chronic inflammation or "smoldering inflammation", 61 and therefore may all promote clonal evolution to MDS (Figure 6). Toll-like receptor (TLR) signaling, an important part of the innate immune system, has been found to be upregulated in MDS, with overexpression of TLRs observed in hematopoietic stem and progenitor cells of patients, compared with agematched controls.…”

Platelet‐to‐lymphocyte ratio and absolute monocyte count have prognostic potential in primary myelodysplastic neoplasms

“…As an alternative, other parameters that contribute to the prognosis of MDS can be explored by using risk systems. A growing consensus shows that inflammation and immunological dysregulation are critical in MDS development, [3][4][5] but the clinical indicators of systemic inflammatory and immunological responses, as well as their prognostic relevance in patients with MDS, have not been well demonstrated.…”