PMID- 8681380 OWN - NLM STAT- MEDLINE DCOM- 19960816 LR - 20191210 IS - 0092-8674 (Print) IS - 0092-8674 (Linking) VI - 85 IP - 6 DP - 1996 Jun 14 TI - An Mll-AF9 fusion gene made by homologous recombination causes acute leukemia in chimeric mice: a method to create fusion oncogenes. PG - 853-61 AB - Homologous recombination in embryonal stem cells has been used to produce a fusion oncogene, thereby mimicking chromosomal translocations that frequently result in formation of tumor-specific fusion oncogenes in human malignancies. AF9 sequences were fused into the mouse Mll gene so that expression of the Mll-AF9 fusion gene occurred from endogenous Mll transcription control elements, as in t(9;11) found in human leukemias. Chimeric mice carrying the fusion gene developed tumors, which were restricted to acute myeloid leukemias despite the widespread activity of the Mll promoter. Onset of perceptible disease was preceded by expansion of ES cell derivatives in peripheral blood. This novel use of homologous recombination formally proves that chromosomal translocations contribute to malignancy and provides a general strategy to create fusion oncogenes for studying their role in tumorigenesis. FAU - Corral, J AU - Corral J AD - Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom. FAU - Lavenir, I AU - Lavenir I FAU - Impey, H AU - Impey H FAU - Warren, A J AU - Warren AJ FAU - Forster, A AU - Forster A FAU - Larson, T A AU - Larson TA FAU - Bell, S AU - Bell S FAU - McKenzie, A N AU - McKenzie AN FAU - King, G AU - King G FAU - Rabbitts, T H AU - Rabbitts TH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cell JT - Cell JID - 0413066 RN - 0 (DNA, Recombinant) RN - 0 (DNA-Binding Proteins) RN - 0 (KMT2A protein, human) RN - 0 (MLLT3 protein, human) RN - 0 (Mllt3 protein, mouse) RN - 0 (Nuclear Proteins) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Transcription Factors) RN - 149025-06-9 (Myeloid-Lymphoid Leukemia Protein) RN - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase) RN - EC 2.1.1.43 (Kmt2a protein, mouse) SB - IM MH - Acute Disease MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - Chimera MH - DNA, Recombinant MH - DNA-Binding Proteins/*genetics MH - Gene Targeting MH - Histone-Lysine N-Methyltransferase MH - Humans MH - Leukemia, Experimental/*genetics MH - Leukemia, Myeloid/blood/pathology MH - Mice MH - Molecular Sequence Data MH - Myeloid-Lymphoid Leukemia Protein MH - Nuclear Proteins/*genetics MH - Oncogenes/*genetics MH - *Proto-Oncogenes MH - Recombinant Fusion Proteins/analysis MH - *Recombination, Genetic MH - Spleen/chemistry MH - Stem Cells MH - Thymus Gland/chemistry MH - *Transcription Factors MH - Translocation, Genetic/genetics EDAT- 1996/06/14 00:00 MHDA- 1996/06/14 00:01 CRDT- 1996/06/14 00:00 PHST- 1996/06/14 00:00 [pubmed] PHST- 1996/06/14 00:01 [medline] PHST- 1996/06/14 00:00 [entrez] AID - S0092-8674(00)81269-6 [pii] AID - 10.1016/s0092-8674(00)81269-6 [doi] PST - ppublish SO - Cell. 1996 Jun 14;85(6):853-61. doi: 10.1016/s0092-8674(00)81269-6.