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Expert Rev Hematol. 2011 Feb;4(1):61-9. doi: 10.1586/ehm.11.2.

Biology and treatment of the 5q- syndrome.

Author information

1
Hematologic Malignancy Division, H Lee Moffitt Cancer Center, Tampa, FL 33612, USA.

Abstract

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, PP2AcĪ± 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.

PMID:
21322779
DOI:
10.1586/ehm.11.2
[Indexed for MEDLINE]

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