title: Deletion 5q MDS: molecular and therapeutic implications.
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.
authors: H Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA. Electronic address: rami.komrokji@moffitt.org.
authors: Rami S
authors: RS
authors: Komrokji
authors: H Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA. Electronic address: eric.padron@moffitt.org.
authors: Eric
authors: E
authors: Padron
authors: Brigham and Women's Hospital, Karp 5.210, 1 Blackfan Circle, Boston, MA 02115, USA. Electronic address: bebert@partners.org.
authors: Benjamin L
authors: BL
authors: Ebert
authors: H Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA. Electronic address: alan.list@moffitt.org.
authors: Alan F
authors: AF
authors: List
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics* / Q000378:metabolism; D004920:Erythropoiesis / Q000187:drug effects / Q000235:genetics; D057895:Haploinsufficiency; D006801:Humans; D000077269:Lenalidomide; D008533:Megakaryocytes / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; C541010:MIRN145 microRNA, human; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; C526722:RPS14 protein, human; D012269:Ribosomal Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D013792:Thalidomide; D000077269:Lenalidomide
keywords: deletion 5q; lenalidomide; myelodysplastic syndromes