Lenalidomide as a disease-modifying agent in patients with del(5q) myelodysplastic syndromes: linking mechanism of action to clinical outcomes.
Lenalidomide as a disease-modifying agent in patients with del(5q) myelodysplastic syndromes: linking mechanism of action to clinical outcomes.
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DOI：
10.1007/s00277-013-1863-5
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发表时间：
2014-01
影响因子：
3.5
通讯作者：
MacBeth, Kyle J.
中科院分区：
文献类型：
--
作者：
Giagounidis, Aristoteles;Mufti, Ghulam J.;Fenaux, Pierre;Germing, Ulrich;List, Alan;MacBeth, Kyle J.
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.
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DOI：
10.3324/haematol.2011.045914
发表时间：
2012-02-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Ades, Lionel;Le Bras, Fabien;Fenaux, Pierre
通讯作者：
Fenaux, Pierre
影响因子：
3.5
作者：
Goehring, Gudrun;Giagounidis, Aristoteles;Schlegelberger, Brigitte
通讯作者：
Schlegelberger, Brigitte
影响因子：
9.8
作者：
Gazda, Hanna T.;Grabowska, Agnieszka;Sieff, Colin A.
通讯作者：
Sieff, Colin A.
影响因子：
64.8
作者：
Ebert, Benjamin L.;Pretz, Jennifer;Bosco, Jocelyn;Chang, Cindy Y.;Tamayo, Pablo;Galili, Naomi;Raza, Azra;Root, David E.;Attar, Eyal;Ellis, Steven R.;Golub, Todd R.
通讯作者：
Golub, Todd R.
影响因子：
3.7
作者：
DeWard AD;Leali K;West RA;Prendergast GC;Alberts AS
通讯作者：
Alberts AS