title: Lenalidomide as a disease-modifying agent in patients with del(5q) myelodysplastic syndromes: linking mechanism of action to clinical outcomes.
abstract: Deletion of the long arm of chromosome 5, del(5q), is the most prevalent cytogenetic abnormality in patients with myelodysplastic syndromes (MDS). In isolation, it is traditionally associated with favorable prognosis compared with other subtypes of MDS. However, owing to the inherent heterogeneity of the disease, prognosis for patients with del(5q) MDS is highly variable depending on the presence of factors such as additional chromosomal abnormalities, >5 % blasts in the bone marrow (BM), or transfusion dependence. Over recent years, the immunomodulatory drug lenalidomide has demonstrated remarkable efficacy in patients with del(5q) MDS. Advances in the understanding of the pathogenesis of the disease have suggested that lenalidomide targets aberrant signaling pathways caused by haplosufficiency of specific genes in a commonly deleted region on chromosome 5 (e.g., SPARC, RPS14, Cdc25C, and PP2A). As a result, the agent specifically targets del(5q) clones while also promoting erythropoiesis and repopulation of the bone marrow in normal cells. This review discusses recent developments in the understanding of the mechanism of action of lenalidomide, and how this underlies favorable outcomes in patients with del(5q) MDS. In addition, we discuss how improved understanding of the mechanism of disease will facilitate clinicians' ability to predict/monitor response and identify patients at risk of relapse.
authors.affiliation: Marienhospital Düsseldorf, Düsseldorf, Germany, gia@krebs-duisburg.de.
authors.forename: Aristoteles
authors.initials: A
authors.lastname: Giagounidis
authors.forename: Ghulam J
authors.initials: GJ
authors.lastname: Mufti
authors.forename: Pierre
authors.initials: P
authors.lastname: Fenaux
authors.forename: Ulrich
authors.initials: U
authors.lastname: Germing
authors.forename: Alan
authors.initials: A
authors.lastname: List
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: MacBeth
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis; D001853:Bone Marrow / Q000187:drug effects; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D002986:Clinical Trials as Topic; D002999:Clone Cells / Q000187:drug effects; D018450:Disease Progression; D004920:Erythropoiesis / Q000187:drug effects*; D018628:Gene Dosage; D016147:Genes, Tumor Suppressor; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000077269:Lenalidomide; D015470:Leukemia, Myeloid, Acute / Q000209:etiology / Q000517:prevention & control; D058990:Molecular Targeted Therapy; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics; D016019:Survival Analysis; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D007155:Immunologic Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D013792:Thalidomide; D000077269:Lenalidomide
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