Down-regulation of the IGF-2/H19 locus during normal and malignant hematopoiesis is independent of the imprinting pattern.
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.
Tessema
Mathewos
M
Institute of Pathology, Medizinische Hochschule Hannover, D-30625 Hannover, Germany.
Länger
Florian
F
Bock
Oliver
O
Seltsam
Axel
A
Metzig
Kathleen
K
Hasemeier
Britta
B
Kreipe
Hans
H
Lehmann
Ulrich
U
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
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