Myelodysplastic Syndromes and Myelodysplastic/Myeloproliferative Neoplasms: An Update on Risk Stratification, Molecular Genetics, and Therapeutic Approaches Including Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Myelodysplastic syndromes are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, peripheral cytopenias, and a variable propensity for leukemic transformation. In recent years there has been an explosion of information on the molecular genetic changes underlying these disorders. This information has substantial prognostic implications, and the influence on therapeutic approaches and the treatment of patients is evolving. Allogeneic hematopoietic stem cell transplantation (alloSCT) is the only known cure for these diseases, but appropriate patient selection is of utmost importance from a risk-benefit perspective. This review focuses on the factors influencing risk stratification in MDS and optimal choice of front-line therapy in the current era, including the interplay of clinical factors and molecular genetic factors, and factors that determine eligibility for alloSCT. The myelodysplastic/myeloproliferative diseases also will be discussed, including the increasing effort to understand the molecular genetics and natural history of these disorders and treatment approaches.

Mutations of myelodysplastic syndromes (MDS): An update

“…In the high-risk group of WHO morphologic categories, higher number of average mutations was consistent with higher degree of clonal expansion, particularly in RAEB1 and RAEB2 subtypes [10,118]. Clinical significance of clonal and subclonal events within the same genes appeared to be similar, and thus emphasizes the clinical importance of mutations in minor subclones, and pivotal role of targeted deep-sequencing of these mutations for understanding the independent and co-existent effects [119].…”

“…Furthermore, cytogenetic picture, which has already been established as the most critical factor in determining survival in 5-tier IPSS-R, would play pivotal role alongside mutation analysis. The importance of cytogenetic aberrations would persist for better monitoring of treatment outcome, especially with allogenic bone marrow transplantation, which is expected to eradicate the malignant hematopoietic clone [118].…”

“…Indeed, the identification of new efficacious inhibitors is a great challenge targeting molecular mutations involved in pathway machineries and disease consequences. Thus, better understanding of epigenetic modification, splicing mechanism and genes/enzymes involved would be important with pharmaceutical value [118]. The sensory activity of TP53 in splicing mechanism demonstrates its importance in mRNA splicing.…”

Myelodysplastic Disorders, 5q-Syndrome

“…Allogeneic HSCT is the only known curative therapeutic option for MDS [2,3,[75][76][77][78][79][80][81][82][83][84]. Not only the rates of allogeneic HSCT to treat MDS are continuously increasing, but also survival rates are steadily improving [76,85]. In patients with MDS, the indications of HSCT are as follows: [3,75,76,81,82].…”

“…Not only the rates of allogeneic HSCT to treat MDS are continuously increasing, but also survival rates are steadily improving [76,85]. In patients with MDS, the indications of HSCT are as follows: [3,75,76,81,82]. Both blast percentage and percentage of cytogenetically abnormal cells reflect MDS disease burden and predict the outcome of HSCT [86].…”