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Deletion 5q MDS: Molecular and therapeutic implications

Authors
  • Komrokji, Rami S.
  • Padron, Eric
  • Ebert, Benjamin L.
  • List, Alan F.1, 2
  • 1 H Lee Moffitt Cancer Center and Research Institute
  • 2 Brigham and Women's Hospital
Type
Published Article
Journal
Best Practice & Research Clinical Haematology
Publisher
Elsevier
Publication Date
Jan 01, 2013
Volume
26
Issue
4
Pages
365–375
Identifiers
DOI: 10.1016/j.beha.2013.10.013
Source
Elsevier
Keywords
License
Unknown

Abstract

Heterozygous, interstitial deletions of chromosome 5q are the most common cytogenetic abnormality in myelodysplastic syndromes (MDS). This chromosomal abnormality is associated with a consistent clinical phenotype, the 5q- syndrome, in a subset of patients, and therapeutic sensitivity to the drug lenalidomide. No genes on chromosome 5q undergo recurrent homozygous inactivation in MDS patients. Instead, haploinsufficiency for key genes powerfully alters hematopoiesis, leading to the MDS phenotype in patients with del(5q). Haploinsufficiency for the RPS14 gene leads to activation of the p53 pathway and the macrocytic anemia characteristic of this disorder, and loss of p53 rescues erythropoiesis and facilitates clonal progression. Other genes, as well as miR-145 and miR-146a, contribute to aberrant megakaryopoiesis and a selective advantage for the del(5q) clone. The integrated effects of haploinsufficiency for these key genes, in aggregate, lead to the full phenotype of the disorder.

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