Activation of MYC in a masked t(8;17) translocation results in an aggressive B-cell leukemia.
Abstract
We have analyzed the oncogene rearrangements involving BCL2 and MYC in the leukemia cells of a patient with an aggressive prolymphocytic leukemia that had an abnormal karyotype including a t(14;18) translocation and a chromosome 17q+. Molecular analysis showed that BCL2 was rearranged in the major breakpoint cluster region and had joined into the immunoglobulin heavy chain gene as in follicular lymphoma. Cloning and sequence analysis of the rearranged MYC gene revealed that MYC was truncated at the Pvu II site at the end of the first exon of MYC and had joined into the regulatory elements of a gene that we called BCL3 (B-cell leukemia/lymphoma 3). The BCL3 locus was mapped to chromosome 17 band q22. We found BCL3 transcribed as a message of 1.7 kilobases in many hematopoietic cell lines representing all hematopoietic lineages. In the patient's leukemia cells, the truncated MYC gene was highly expressed under the influence of BCL3 regulatory elements, leading to an aggressive B-cell leukemia that presumably had been derived from an indolent lymphoma carrying a rearranged BCL2 gene.
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mir-142s/mir-142as are located in the junction of the t(8;17) chromosomal rearrangement, which fuses Bcl3 and Myc genes and results in an aggressive B-cell leukemia.
“Notably, mir-142s/mir-142as are located in the junction of the t(8;17) chromosomal rearrangement. This translocation fuses Bcl3 and Myc genes, thus resulting in an aggressive B-cell leukemia [2,37].”
From Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation (2004) · cites this paper as [37]
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Sempere, L. F., Freemantle, S., Pitha-Rowe, I., Moss, E., Dmitrovsky, E., & Ambros, V. (2004) · Genome Biology · doi:10.1186/gb-2004-5-3-r13 · Cited by 1,578 · see citing works
MicroRNAs and immunity: Novel players in the regulation of normal immune function and inflammation
Sonkoly, E., Ståhle, M., & Pivarcsi, A. (2008) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2008.01.005 · Cited by 523 · see citing works
- Authors
- Gauwerky, C. E., Huebner, K., Isobe, M., Nowell, P. C., & Croce, C. M.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1989-11
- Volume
- 86
- Issue
- 22
- Pages
- 8867-8871
- ISSN
- 0027-8424
- 1091-6490
- Cited by
- 97
- References
- 1
- Language
- en
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