title: Down-regulation of the IGF-2/H19 locus during normal and malignant hematopoiesis is independent of the imprinting pattern.
abstract: H19 and IGF-2 are two growth regulatory genes located on chromosome 11p15 implicated in tumorigenesis. Both genes are imprinted and regulated reciprocally under many circumstances. In order to elucidate the contribution of H19 and IGF-2 to leukemogenesis, the mRNA expression level of both genes were quantitated in bone marrow biopsies and peripheral blood samples from normal (n=98), chronic myelomonocytic leukemia (CMML, n=43), chronic myelogenous leukemia (CML, n=40) and, acute myelogenous leukemia (AML, n=32) cases. A concomitant reduction of H19 and IGF-2 expression was observed in all leukemic samples compared to the healthy controls. This down-regulation was not accompanied by changes in methylation of the differentially methylated region (DMR). Whereas the H19 gene showed strict monoallelic expression in all informative normal (n=31) and leukemic (n=54) samples, the imprinting pattern of the IGF2 gene was found to be heterogeneous. No correlations between imprinting status (mono- versus biallelic expression), quantitative mRNA expression levels and course of disease were found for the IGF-2 gene. The data suggest a disturbed regulation of the IGF-2/H19 locus in myeloid leukemias which is not caused by loss of imprinting.
authors.affiliation: Institute of Pathology, Medizinische Hochschule Hannover, D-30625 Hannover, Germany.
authors.forename: Mathewos
authors.initials: M
authors.lastname: Tessema
authors.forename: Florian
authors.initials: F
authors.lastname: Länger
authors.forename: Oliver
authors.initials: O
authors.lastname: Bock
authors.forename: Axel
authors.initials: A
authors.lastname: Seltsam
authors.forename: Kathleen
authors.initials: K
authors.lastname: Metzig
authors.forename: Britta
authors.initials: B
authors.lastname: Hasemeier
authors.forename: Hans
authors.initials: H
authors.lastname: Kreipe
authors.forename: Ulrich
authors.initials: U
authors.lastname: Lehmann
mesh_terms: D000483:Alleles; D001706:Biopsy; D001854:Bone Marrow Cells / Q000378:metabolism; D019175:DNA Methylation; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D018392:Genomic Imprinting; D005838:Genotype; D006410:Hematopoiesis / Q000235:genetics*; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis* / Q000235:genetics*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D015477:Leukemia, Myelomonocytic, Chronic / Q000235:genetics; D008957:Models, Genetic; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000378:metabolism; D022661:RNA, Untranslated / Q000096:biosynthesis* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018076:DNA, Complementary; C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D022661:RNA, Untranslated; D007335:Insulin-Like Growth Factor II