| Biology and treatment of the 5q- syndrome. | |
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MedLine Citation:
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PMID: 21322779 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The 5q- syndrome is a unique subtype of myelodysplastic syndromes typified by a relatively indolent course and responsiveness to lenalidomide. Here, we review the salient biologic features of this disease. Hemizygous deletion of a segment of chromosome 5q is believed to be the disease-initiating event. Recent molecular techniques have isolated the common deleted region and characterized key candidate genes contributing to the disease phenotype. Gene-specific RNA interference strategies revealed that haplo-insufficiency for the RPS14 gene, which encodes a ribosomal protein, is a critical effector of the p53-dependent erythroid hypoplasia and apoptotic loss of erythroid precursors. Disease-specific sensitivity to lenalidomide results from the drug's inhibitory effect on two haplodeficient phosphatases, PP2Acα and CDC25c, which are coregulators of the G(2)/M checkpoint. Hyperphosphorylation of MDM2, as a result of inhibition of PP2A phosphatase activity, stabilizes MDM2, permitting p53 degradation and transition to G(2) arrest and clonal suppression. With the emerging data elucidating the pathogenesis of the 5q- syndrome and the success of clinical trials, a cohesive story connecting the biology and pharmacology associated with this subtype of myelodysplastic syndromes has emerged. |
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Authors:
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Eric Padron; Rami Komrokji; Alan F List |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Expert review of hematology Volume: 4 ISSN: 1747-4094 ISO Abbreviation: Expert Rev Hematol Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-02-16 Completed Date: 2011-05-27 Revised Date: 2011-12-06 |
Medline Journal Info:
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Nlm Unique ID: 101485942 Medline TA: Expert Rev Hematol Country: England |
Other Details:
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Languages: eng Pagination: 61-9 Citation Subset: IM |
Affiliation:
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Hematologic Malignancy Division, H Lee Moffitt Cancer Center, Tampa, FL 33612, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Anemia, Macrocytic*
/
genetics,
metabolism,
therapy Antineoplastic Agents / therapeutic use Chromosome Deletion* Chromosomes, Human, Pair 5 / genetics, metabolism Clinical Trials as Topic Gene Deletion Humans Thalidomide / analogs & derivatives, therapeutic use |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 191732-72-6/lenalidomide; 50-35-1/Thalidomide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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