Alternative titles; symbols
HGNC Approved Gene Symbol: ELL
Cytogenetic location: 19p13.11 Genomic coordinates (GRCh38) : 19:18,442,663-18,522,070 (from NCBI)
Thirman et al. (1994) cloned the gene that fuses to MLL (159555) in patients with acute myeloid leukemia associated with the translocation t(11;19)(q23;p13.1). This translocation is distinct from another type of 11;19 translocation with a 19p13.3 breakpoint that results in the fusion of MLL to the ENL gene (159556). By PCR screening of a cDNA library prepared from a patient's leukemia cells with this translocation, Thirman et al. (1994) obtained a fusion transcript containing exon 7 of MLL and sequence of an unknown gene. The sequence of this gene was amplified and used as a probe to screen a fetal brain cDNA library. On Northern blot analysis, this cDNA detected a 4.4-kb transcript that was abundant in peripheral blood leukocytes, skeletal muscle, placenta, and testis and expressed at lower levels in spleen, thymus, heart, brain, lung, kidney, liver, and ovary. In addition, a 2.8-kb transcript was present in peripheral blood, testis, and placenta. On zoo blots, this gene was shown to be evolutionarily conserved in 10 mammalian species, as well as in chicken, frog, and fish. They named the gene ELL (for 'eleven-nineteen lysine-rich leukemia' gene). A highly basic, lysine-rich motif of the predicted ELL protein was homologous to similar regions of several proteins, including the DNA-binding domain of poly(ADP-ribose) polymerase (173870).
ELL was shown by Shilatifard et al. (1996) to encode an elongation factor that can increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA. The authors noted that ELL is the second elongation factor to be implicated in oncogenesis (elongin (see 600786), which is a transcription factor regulated by the product of the von Hippel-Lindau (VHL) tumor suppressor gene (608537), was the first), and they stated that these findings provide further support for a close connection between the regulation of transcription and cell growth.
In studies of the transforming properties of the MLL-ELL fusion gene, Lavau et al. (2000) retrovirally transduced primary murine hematopoietic progenitors and assessed their growth properties both in vitro and in vivo. MLL-ELL increased the proliferation of myeloid colony-forming cells in methylcellulose cultures upon serial replating, whereas overexpression of ELL alone had no effect. Reconstitution of lethally irradiated congenic mice with bone marrow progenitors transduced with MLL-ELL resulted in the development of monoclonal or pauciclonal acute myeloid leukemias within 100 to 200 days. The leukemic cells were readily transplantable to secondary recipients and could be established as immortalized cell lines in liquid cultures.
Lavau, C., Luo, R. T., Du, C., Thirman, M. J. Retrovirus-mediated gene transfer of MLL-ELL transforms primary myeloid progenitors and causes acute myeloid leukemias in mice. Proc. Nat. Acad. Sci. 97: 10984-10989, 2000. [PubMed: 10995463] [Full Text: https://doi.org/10.1073/pnas.190167297]
Shilatifard, A., Lane, W. S., Jackson, K. W., Conaway, R. C., Conaway, J. W. An RNA polymerase II elongation factor encoded by the human ELL gene. Science 271: 1873-1876, 1996. [PubMed: 8596958] [Full Text: https://doi.org/10.1126/science.271.5257.1873]
Thirman, M. J., Levitan, D. A., Kobayashi, H., Simon, M. C., Rowley, J. D. Cloning of ELL, a gene that fuses to MLL in a t(11;19)(q23;p13.1) in acute myeloid leukemia. Proc. Nat. Acad. Sci. 91: 12110-12114, 1994. [PubMed: 7991593] [Full Text: https://doi.org/10.1073/pnas.91.25.12110]