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 resultin g in differential allelic expression of a gene and plays an important role in the development of certain types of cancer and genetic disease s. Imprinting of IGF2 was demonstrated in normal placenta and fetal ki dney by showing monoallelic paternal expression. In contrast, several kinds of tumor showed biallelic expression of IGF2, suggesting that re laxation of the normal imprinting of this growth cytokine may be a fea ture of some tumors, In this study we wished to determine whether rela xation of IGF2 imprinting was also common in human leukemias. An intra genic 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 a ssay. RNA-PCR from these informative leukemia samples studied showed b iallelic expression of IGF2, indicating loss of normal imprinting of t his gene to be very frequent. In conclusion, constitutional loss of mo noallelic expression in 50% of the leukemia samples tested suggests th at abnormal imprinting of IGF2 could play an important role in either leukemogenesis or cytokine dysregulation for leukemic cells. (C) 1997 Academic Press.