AMPLIFICATION OF THE E2F1 TRANSCRIPTION FACTOR GENE IN THE HEL ERYTHROLEUKEMIA CELL-LINE

The E2F transcription factor plays an important regulatory role in cel l proliferation, mediating the expression of genes whose products are essential for inducing resting cells to enter the cell cycle and synth esize DNA. To investigate the possible involvement of E2F in hematopoi etic malignancies, we isolated genomic clones encompassing the human E 2F1 gene. We then used fluorescence in situ hybridization to localize E2F1 to human chromosome 20q11, telomeric to the p107 locus, a gene wh ose product is related to the retinoblastoma gene product (pRb). This finding contrasts with the 1p36 and 6q22 chromosomal locations previou sly assigned E2F2 and E2F3, two additional members of the E2F family. Although deletions or structural rearrangements of E2F1 were not detec ted in 14 primary acute leukemia or myelodysplasia samples with struct ural abnormalities of chromosome 20q11, the gene was amplified and ove rexpressed in HEL erythroleukemia cells and translocated to other chro mosomes in several established human leukemia cell lines. This study p rovides the first evidence of gene amplification involving a member of the E2F family of transcription factors. We propose that E2F1 overexp ression in erythroid progenitors may stimulate abnormal cell prolifera tion by overriding negative regulatory signals mediated by tumor suppr essor proteins such as pRb. (C) 1995 Academic Press, Inc.