%0 Journal Article
%T Important Genes in the Pathogenesis of 5q- Syndrome and Their Connection with Ribosomal Stress and the Innate Immune System Pathway
%A Ota Fuchs
%J Leukemia Research and Treatment
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/179402
%X 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 integration 1 (Fli1) is one of the target genes of miR145. Increased Fli1 expression enables effective megakaryopoiesis in 5q-syndrome. 1. Introduction Approximately 15% of patients with MDS have abnormalities of chromosome 5 [1]. These abnormalities include interstitial deletion of a segment of the long arm of chromosome 5q [del(5q), 5q-syndrome], monosomy, and unbalanced translocations. 5q-syndrome as MDS category was defined by the World Health Organization (WHO) [2], and it is characterized by refractory macrocytic anemia with dyserythropoiesis, transfusion dependence, normal to elevated platelet counts, hypolobated and nonlobated megakaryocytes, female preponderance, a favourable prognosis, and low risk of progression to AML compared with other types of MDS [3¨C10]. Many research groups analysed chromosome 5q deletions in patients with 5q-syndrome. We will shortly describe these studies from historical point of view and not for relevance in the pathogenesis. Deletion of interferon regulatory factor-1 gene (IRF1) mapped to chromosome 5q31 was detected [11]. IRF1 is a putative tumor suppressor and a transcriptional activator of interferon and interferon-stimulated genes. IRF1 dosage experiments demonstrated that 2 patients with 5q-syndrome retained both copies of this gene [12]. Thus, IRF1 maps outside the common deleted segment of the 5q-chromosome, and the same result was obtained in the case of EGR1 (epidermal growth receptor 1) [13, 14]. Molecular mapping techniques defined the region of gene loss in two patients with the 5q-syndrome and uncharacteristically small 5q deletions (5q31¨Cq33) [14]. The allelic loss of 10 genes localized to 5q23-qter [centromere-CSF2 (colony-stimulating factor 2/granulocyte-macrophage/)-EGR1 (early growth
%U http://www.hindawi.com/journals/lrt/2012/179402/