Loss of imprinting of IGF-II gene in children with acute lymphoblastic leukemia
DOI: 10.1016/S0145-2126(03)00014-6
Title: Loss of imprinting of IGF-II gene in children with acute lymphoblastic leukemia
Journal Title: Leukemia Research
Volume: 27
Issue: 9
Publication Date: September 2003
Start Page: 807
End Page: 812
Published online: online 18 February 2003
ISSN: 0145-2126
Author: Peter Vorwerka, Heike Wexa, Cornelia Besserta, Bianka Hohmanna, Uwe Schmidtb, Uwe Mittlera

  • a Department of Pediatric Oncology, Otto von Guericke University, Emanuel-Larisch-Weg 17-19, D-39112 Magdeburg, Germany

  • b Institute of Biometrics and Medical Informatics, Otto von Guericke University, Leipziger Straße 44, D-39112 Magdeburg, Germany
  • Abstract: like growth factor-II (IGF-II) is known to be involved in the regulation of growth, differentiation and cell death in normal human tissues. In a variety of human tumors, the IGF-II gene is overexpressed and considered to be a stimulator for tumor growth through autocrine and paracrine mechanisms. The IGF-II gene is normally parental imprinted, only the paternal allele being expressed in most tissues. Several reports about biallelic expression (Loss of imprinting (LOI)) of the IGF-II gene in different tumors suggest a role of dysregulation of IGF-II imprinting in tumorigenesis. However, biallelic expression of IGF-II gene has also been reported in different tissues of a significant number of normal controls, indicating either a normal phenomenon or an elevated cancer risk in this group of persons. Although LOI of IGF-II presumably promotes tumorigenesis by increasing IGF-II expression, elevated IGF-II levels in those patients have not been reported.We studied IGF-II gene expression in malignant lymphoblasts of 124 children suffering from acute lymphoblastic leukemia, 196 cord blood samples from healthy newborns and mononuclear cells (MNC) from 50 healthy age matched children. The ApaI polymorphism in exon 9 of the IGF-II gene and allele-specific exon-connection RT-PCR was used for determination of the imprinting status. From 44 informative ALL-patients, 24 (54%) showed LOI of the IGF-II gene. Twenty percent of the informative cord blood samples (N=56) and 14% of the informative MNC samples from healthy controls (N=22) showed biallelic expression of IGF-II. In the ALL-patients, no statistical significant correlation between LOI patients and relapse rate, surviving rate and risk groups could be detected.We conclude that LOI of IGF-II occurs in malignant lymphoblasts of children suffering from acute lymphoblastic leukemia in more than 50% of the patients. In MNC from cord blood and peripheral MNC from healthy controls, biallelic expression could be detected in up to 20% of all cases. The importance of LOI in ALL-patients needs to be further evaluated to determine its impact in leukemogenesis.
    Accepted: 21 December 2002
    Received: 17 June 2002
    Abbreviations: ALL, acute lymphoblastic leukemia; AML, acute myelogenous leukemia; ASA, allele-specific amplification; BFM, Berlin–Frankfurt–Münster; CML, chronic myelogenous leukemia; FAB, French–American–British; IGFBP, insulin-like growth factor binding protein; IGF-II, insulin-like growth factor-II; LOI, loss of imprinting; MNC, mononuclear cells
    Tel: +49-391-6717223
    Fax: +49-391-67190562
    Email: peter.vorwerk@medizin.uni

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