Epidemiology and Pathogenesis of Myelodysplastic Syndrome

Abstract

Myelodysplastic syndrome (MDS) is a clonal disorder characterized by ineffective hematopoiesis and variable cytopenias with a considerable risk of progression to acute myeloid leukemia. Epidemiological assessment of MDS remains challenging because of evolving classification systems, but the overall incidence in the United States is estimated to be approximately 4 per 100,000 and increases with age. The sequential accumulation of mutations drives disease evolution from asymptomatic clonal hematopoiesis (CH) to CH of indeterminate potential, clonal cytopenia of unknown significance, to frank MDS. The molecular heterogeneity seen in MDS is highly complex and includes mutations of genes involved in splicing machinery, epigenetic regulation, differentiation, and cell signaling. Recent advances in the understanding of the molecular landscape of MDS have led to the development of improved risk assessment tools and novel therapies. Therapies targeting the underlying pathophysiology will hopefully further expand the armamentarium of MDS therapeutics, bringing us closer to a more individualized therapeutic approach based on the unique molecular profile of each patient and eventually improving the outcomes of patients with MDS. We review the epidemiology of MDS and the newly described MDS precursor conditions CH, CH of indeterminate potential, and CCUS. We then discuss central aspects of MDS pathophysiology and outline specific strategies targeting hallmarks of MDS pathophysiology, including ongoing clinical trials examining the efficacy of these therapeutic modalities.

Atranorin is a novel potential candidate drug for treating myelodysplastic syndrome

“…Other interactions, their dynamics and impact varied depending on the AKT homolog, but the common interacting interface can be revealed within the allosteric site mainly via cumulative hydrophobic interactions, H-bonds and water-bridges (Figs. [17][18][19][20]. The main binding pattern of AKT1 within the allosteric sites was Asn53, Ser56, Glu79, Thr80, Thr211, Leu264, Val270, Tyr272, Asp292.…”

“…Myelodysplastic syndrome accounts for about 1 % of all malignant diseases, but is nevertheless associated with significant mortality. For example, in Europe and the USA, epidemiological assessment of the disease remains challenging due to the development of classification systems, but the overall incidence is about five cases per 100,000 people per year after 60 years of age and increases with age [20][21][22] .…”

The Role of Hepcidin in Myelodysplastic Syndromes (MDS): A Systematic Review of Observational Studies

“…2 The authors did not specify which form of hepcidin (serum, bone marrow) their results referred to. 3 The authors originally measured ferritin levels using the unit ng/mL; however, for standardization, the results in Table 2 are expressed in µg/L. Abbreviations: BM = bone marrow; CMML = chronic myelomonocytic leukemia; ELISA = enzyme-linked immunosorbent assay; MDS = myelodysplastic syndromes; MDS-U = unclassified myelodysplastic syndromes; ND = not determined; RA = refractory anemia; RAEB = refractory anemia with excess blasts; RAEB-1 = refractory anemia with excess blasts type 1; RAEB-2 = refractory anemia with excess blasts type 2; RARS = refractory anemia with ringed sideroblasts; RCMD = refractory cytopenia with multilineage dysplasia; RCUD = refractory cytopenia with unilineage dysplasia; SELDI-TOF MS = surface-enhanced laser-desorption/ionization time-of-flight mass spectrometry.…”

“…2 Data were available for 20 patients. 3 The authors defined refractory cytopenia with unilineage dysplasia/refractory anemia with ring sideroblasts/5q-syndrome/refractory cytopenia with multilineage dysplasia as a low-risk group. 4 The authors originally measured hepcidin levels using the mg/L unit; however, for standardization, the results in Table 4 are expressed in ng/mL.…”

“…Myelodysplastic syndromes (MDS) are a group of clonal hematologic neoplasms characterized by impaired hematopoietic stem cell (HSC) differentiation and inefficient hematopoiesis in the bone marrow [1,2]. In the United States, there are approximately 4 per 100,000 new cases reported annually and in Europe, this number is believed to be twice as high [3,4]. The heterogeneity of the disease and its remarkably intricate pathophysiology mean that, despite advancements in understanding the molecular basis of MDS, its etiology is known in only about 15% of cases [5].…”