Mutations in myelodysplastic syndromes: Core abnormalities and CHIPping away at the edges

The myelodysplastic syndromes myelodysplastic syndromes: (my-eh-lo-diss-PLASS-tik SIN-dromez) A group of disorders where the bone marrow does not work well, and the bone marrow cells fail to make enough healthy blood cells. Myelo refers to the bone marrow. Dysplastic means abnormal growth or development. People with MDS have low blood cell count for at… (MDS) are a heterogeneous constellation of hematologic malignancies characterized by aberrant differentiation and clonal expansion of abnormal myeloid cells that initially manifest with ineffective hematopoiesis hematopoiesis: (hi-mat-uh-poy-EE-suss) The process of making blood cells in the bone marrow. and consequent cytopenias. The prognosis of MDS is variable and depends on clinical and hematologic parameters, cytogenetic and molecular findings, as well as comorbidities. Gene sequencing studies have uncovered remarkable genomic complexity within MDS, based on the presence of recurrent and sometimes co-operating mutations in genes encoding proteins that play a role in numerous biologic pathways. Although the treatment of MDS is currently limited to the use of hypomethylating, immunomodulatory, or erythropoiesis-stimulating agents, improved understanding of the molecular underpinnings of its pathophysiology pathophysiology: Functional changes in the bodies that are associated with or result from disease or injury. has led to the development of multiple targeted treatments that are poised to be added to the therapeutic armamentarium. This review will focus on the role of mutations in the pathogenesis, diagnosis, and prognosis of MDS and how the discovery of clonal hematopoiesis of indeterminate potential (CHIP) might impact the utility of detecting mutations in the diagnosis of MDS.