Past, present and future in low-risk myelodysplastic syndrome

Abstract

Myelodysplastic syndromes (MDS) is a heterogeneous group of disorders characterized by increased risk of acute myeloid leukemia transformation and cytopenia. The prognosis of MDS patients can be evaluated with various scoring systems, the most commonly used are IPSS (International Prognostic Scoring System), revised-IPSS, and WPSS (WHO classification-based prognostic scoring system). MDS treatment is decided according to the risk classification. The goal of treatment in low-risk MDS is to improve cytopenia, reduce transfusion needs, improve quality of life, prolong overall survival, and maybe reduce the risk of progression to leukemia. In the near future, combining both genomics-based, ex vivo functional based and molecular stratification analysis will lead the way to a personalized and targeted approach.

Keywords: anemia; low risk; myelodysplastic syndrome; thrombocytopenia; treatment.

FIGURE 1

Mechanism of actions for treatments in low-risk myelodysplastic syndromes (MDS). Erythropoiesis stimulating agents stimulate gene transcription of maturation and proliferation of erythrocytes through JAK/STAT and Erk1/2. Lenalidomide inhibits the CDC25C phosphatase and by decrease in CK1α levels. Inhibition of the CDC25C phosphatase leads to a stoppage of proliferation by induction of an arrest in the cell cycle at the transition between G2 and M phase. Hypomethylating agents induce DNA hypomethylation. Ivosidenib, and enasidenib inhibits IDH1 or 1DH2 genes. Thrombopoietic receptor agonists activate signaling leads to increased platelet production. Imetelstat is a drug that help maintaining normal hematopoiesis by acting as a telomerase inhibitor in cells with short telomere length and hyper telomerase activity. “Luspatercept” and “sotatercept” specific activin receptor fusion proteins that act as ligand traps to neutralize negative regulators of late-stage erythropoiesis. Roxadustat is a small molecule that can be used orally and is an inhibitor of the “hypoxia-inducible factor” (, , –64). EPO-R, erythropoietin receptor; JAK, janus kinase; STAT, signal transducer and activator of transcription; TPO-R, thrombopoietin receptor.

FIGURE 2

Current treatment approaches in low-risk myelodysplastic syndromes (MDS) (19, 20). MDS, myclodysplastic syndrome; IPSS, International Prognostic Scoring System; R-IPSS, Revised International Prognostic Scoring System; TPO, thrombopoietin; EPO, erythropoietin; ESA, erythropoiesis stimulating agents; G-CSF, granulocyte colony stimulating factor; HMA, hypomethylating agents; AHSCT, allogeneic hematopoietic stem cell transplantation; ATG, antithymocyte globulin; CsA, cyclosporine.