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Best Pract Res Clin Haematol. 2013 Dec;26(4):365-75. doi: 10.1016/j.beha.2013.10.013. Epub 2013 Oct 16.

Deletion 5q MDS: molecular and therapeutic implications.

Author information

1
H Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA. Electronic address: rami.komrokji@moffitt.org.
2
H Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA. Electronic address: eric.padron@moffitt.org.
3
Brigham and Women's Hospital, Karp 5.210, 1 Blackfan Circle, Boston, MA 02115, USA. Electronic address: bebert@partners.org.
4
H Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA. Electronic address: alan.list@moffitt.org.

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.

KEYWORDS:

deletion 5q; lenalidomide; myelodysplastic syndromes

PMID:
24507813
DOI:
10.1016/j.beha.2013.10.013
[Indexed for MEDLINE]

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