CLONING OF ELL, A GENE THAT FUSES TO MLL IN A T(11-19)(Q23-P13.1) IN ACUTE MYELOID-LEUKEMIA

To characterize the functions of MLL fusion transcripts, we cloned the gene that fuses to MLL in the translocation t(11;19)(q23;p13.1). This translocation is distinct from another type of 11;19 translocation wi th a 19p13.3 breakpoint that results in the fusion of MLL to the ENL g ene. By PCR screening of a cDNA library prepared from a patient's leuk emia cells with this translocation, we obtained a fusion transcript co ntaining exon 7 of MLL and sequence of an unknown gene. The sequence o f 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 t ranscript that was abundant in peripheral blood leukocytes, skeletal m uscle, placenta, and testis and expressed at lower levels in spleen, t hymus, 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. We have named this gene ELL (for eleven-nineteen lysine-rich leukemia gene). A highly basic, lysine-rich moth of the predicted ELL protein is homol ogous to similar regions of several proteins, including the DNA-bindin g domain of poly(ADP-ribose) polymerase. The characterization of the n ormal functions of ELL as well as its altered function when fused to M LL will be critical to further our understanding of the mechanisms of leukemogenesis.