Important Genes in the Pathogenesis of 5q- Syndrome and Their Connection with Ribosomal Stress and the Innate Immune System Pathway.pdfVIP

Hindawi Publishing Corporation Leukemia Research and Treatment Volume 2012, Article ID 179402, 14 pages doi:10.1155/2012/179402 Review Article Important Genes in the Pathogenesis of 5q- Syndrome and Their Connection with Ribosomal Stress and the Innate Immune System Pathway Ota Fuchs1, 2 1 Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128 20 Prague 2, Czech Republic 2 Center of Experimental Hematology, First Medical Faculty, Charles University, Institute of Pathological Physiology, 128 53 Prague 2, Czech Republic Correspondence should be addressed to Ota Fuchs, ota.fuchs@uhkt.cz Received 25 September 2011; Revised 6 November 2011; Accepted 14 November 2011 Academic Editor: Daniela Cilloni Copyright © 2012 Ota Fuchs. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Myelodysplastic syndrome (MDS) with interstitial deletion of a segment of the long arm of chromosome 5q [del(5q)] is characterized by bone marrow erythroid hyperplasia, atypical megakaryocytes, thrombocythemia, refractory anemia, and low risk of progression to acute myeloid leukemia (AML) compared with other types of MDS. The long arm of chromosome 5 contains two distinct commonly deleted regions (CDRs). The more distal CDR lies in 5q33.1 and contains 40 protein-coding genes and genes coding microRNAs (miR-143, miR-145). In 5q-syndrome one allele is deleted that accounts for haploinsufficiency of these genes. The mechanism of erythroid failure appears to involve the decreased expression of the ribosomal protein S14 (RPS14) gene and the upregulation of the p53 pathway by ribosomal stress. Friend leukemia virus integr