Loss of Imprinting of Human Insulin-like Growth Factor II Gene, IGF2, in Acute Myeloid Leukemia

Genomic imprinting is a non-Mendelian form of gene regulation resulting in differential allelic expression of a gene and plays an important role in the development of certain types of cancer and genetic diseases. Imprinting of IGF2 was demonstrated in normal placenta and fetal kidney by showing monoallelic paternal expression. In contrast, several kinds of tumor showed biallelic expression of IGF2, suggesting that relaxation of the normal imprinting of this growth cytokine may be a feature of some tumors. In this study we wished to determine whether relaxation of IGF2 imprinting was also common in human leukemias. An intragenic Apa I polymorphism within the 3' untranslated region of the gene was used to examine allele-specific transcription in leukemic blasts derived from 24 primary patients with acute myeloid leukemia by RT-PCR. Leukemic samples from 12 of the 24 leukemia patients were identified as heterozygous for IGF2 and potentially informative for the RT-PCR assay. RNA-PCR from these informative leukemia samples studied showed biallelic expression of IGF2, indicating loss of normal imprinting of this gene to be very frequent. In conclusion, constitutional loss of monoallelic expression in 50% of the leukemia samples tested suggests that abnormal imprinting of IGF2 could play an important role in either leukemogenesis or cytokine dysregulation for leukemic cells.