Lenalidomide as a disease-modifying agent in patients with del(5q) myelodysplastic syndromes: linking mechanism of action to clinical outcomes.

Articles MDS published on April 21, 2014

Giagounidis A, et al. Lenalidomide as a disease-modifying agent in patients with del(5q) myelodysplastic syndromes: linking mechanism of action to clinical outcomes. Ann Hematol. 2014;93:1-11.

The most prevalent cytogenetic abnormality in myelodysplastic syndrome (MDS) is a partial deletion of the long arm of chromosome 5, del(5q), which is present in about 15% of cases. While such patients typically have a favorable prognosis compared with other subtypes of MDS, other adverse factors (such as additional chromosomal abnormalities) may change this course. Recently, lenalidomide has shown robust efficacy in patients with del(5q) MDS, possibly by targeting aberrant signaling pathways caused by haplosufficiency of specific genes in a commonly deleted region on chromosome 5. As a result, lenalidomide specifically targets del(5q) clones while also promoting erythropoiesis and repopulation of bone marrow in normal cells. This is important because most patients with del(5q) become dependent on transfusion of red blood cells.

The article by Giagounidis, et al. takes a detailed look at the pathogenesis of del(5q) MDS and the molecular basis for impaired erythropoiesis, thrombocytosis and neutropenia, clonal dominance of del(5q) progenitors, and the heterogeneity of the del(5q) subpopulation. The characteristics of these patients rend them particularly sensitive to lenalidomide, and the authors eloquently describe the drug’s effect on multiple genes and their functional pathways, linking the mechanisms of action with observed clinical outcomes.

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Last modified: May 23, 2014

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