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Acute mixed-lineage leukemia t(4;11)(q21;q23) generates an MLL-AF4 fusion product.
Open accessAbstract
A chromosomal translocation, t(4;11)-(q21;q23), is associated with an aggressive mixed-lineage leukemia. A yeast artificial chromosome was used to clone the chromosomal breakpoint of this translocation in the RS4;11 cell line. The breakpoint sequences revealed an inverted repeat bordered by a consensus site for topoisomerase II binding and cleavage as well as chi-like elements. The der(11) chromosome encodes a fusion RNA and predicted chimeric protein between the 11q23 gene MLL and a 4q21 gene designated AF4. The sequence of the complete open reading frame for this fusion transcript reveals the MLL protein to have homology with DNA methyltransferase, the Drosophila trithorax gene product, and the "AT-hook" motif of high-mobility-group proteins. An alternative splice that deletes the AT-hook region of MLL was identified. AF4 is a serine- and proline-rich putative transcription factor with a glutamine-rich carboxyl terminus. The composition of the complete MLL-AF4 fusion product argues that it may act through either a gain-of-function or a dominant negative mechanism in leukemogenesis.
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Cited by
Transcription Factors, Normal Myeloid Development, and Leukemia
Tenen, D. G., Hromas, R., Licht, J. D., & Zhang, D.-E. (1997) · Blood · doi:10.1182/blood.v90.2.489 · Cited by 735
Leukemia in twins: lessons in natural history
Greaves, M. F., Maia, A. T., Wiemels, J. L., & Ford, A. M. (2003) · Blood · doi:10.1182/blood-2002-12-3817 · Cited by 543
Corral, J., Lavenir, I., Impey, H., Warren, A. J., Forster, A., Larson, T. A., Bell, S., McKenzie, A. N. J., King, G., & Rabbitts, T. H. (1996) · Cell · doi:10.1016/s0092-8674(00)81269-6 · Cited by 522
Chromatin modifier enzymes, the histone code and cancer
Santos-Rosa, H., & Caldas, C. (2005) · European Journal of Cancer · doi:10.1016/j.ejca.2005.08.010 · Cited by 337
Lee, J.-H., & Skalnik, D. G. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508312200 · Cited by 332
Metadata
- Authors
- Domer, P. H., Fakharzadeh, S. S., Chen, C. S., Jockel, J., Johansen, L., Silverman, G. A., Kersey, J. H., & Korsmeyer, S. J.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1993-08-15
- Volume
- 90
- Issue
- 16
- Pages
- 7884-7888
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2091260442
- Cited by
- 226
- References
- 0
- FWCI
- 6.94
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Acute mixed-lineage leukemia t(4;11)(q21;q23) generates an MLL-AF4 fusion product. https://app.cochat.ai/papers/10.1073/pnas.90.16.7884
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- Domer, P. H., Fakharzadeh, S. S., Chen, C. S., Jockel, J., Johansen, L., Silverman, G. A., Kersey, J. H., & Korsmeyer, S. J. (1993). Acute mixed-lineage leukemia t(4;11)(q21;q23) generates an MLL-AF4 fusion product. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.90.16.7884
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