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. 1989 Nov;86(22):8867–8871. doi: 10.1073/pnas.86.22.8867

Activation of MYC in a masked t(8;17) translocation results in an aggressive B-cell leukemia.

C E Gauwerky 1, K Huebner 1, M Isobe 1, P C Nowell 1, C M Croce 1
PMCID: PMC298391  PMID: 2682663

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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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  2. Coussens L., Parker P. J., Rhee L., Yang-Feng T. L., Chen E., Waterfield M. D., Francke U., Ullrich A. Multiple, distinct forms of bovine and human protein kinase C suggest diversity in cellular signaling pathways. Science. 1986 Aug 22;233(4766):859–866. doi: 10.1126/science.3755548. [DOI] [PubMed] [Google Scholar]
  3. Croce C. M. Role of chromosome translocations in human neoplasia. Cell. 1987 Apr 24;49(2):155–156. doi: 10.1016/0092-8674(87)90552-6. [DOI] [PubMed] [Google Scholar]
  4. Dayton A. I., Selden J. R., Laws G., Dorney D. J., Finan J., Tripputi P., Emanuel B. S., Rovera G., Nowell P. C., Croce C. M. A human c-erbA oncogene homologue is closely proximal to the chromosome 17 breakpoint in acute promyelocytic leukemia. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4495–4499. doi: 10.1073/pnas.81.14.4495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. De Jong D., Voetdijk B. M., Beverstock G. C., van Ommen G. J., Willemze R., Kluin P. M. Activation of the c-myc oncogene in a precursor-B-cell blast crisis of follicular lymphoma, presenting as composite lymphoma. N Engl J Med. 1988 May 26;318(21):1373–1378. doi: 10.1056/NEJM198805263182106. [DOI] [PubMed] [Google Scholar]
  6. Dierks P., van Ooyen A., Cochran M. D., Dobkin C., Reiser J., Weissmann C. Three regions upstream from the cap site are required for efficient and accurate transcription of the rabbit beta-globin gene in mouse 3T6 cells. Cell. 1983 Mar;32(3):695–706. doi: 10.1016/0092-8674(83)90055-7. [DOI] [PubMed] [Google Scholar]
  7. Erikson J., Finan J., Nowell P. C., Croce C. M. Translocation of immunoglobulin VH genes in Burkitt lymphoma. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5611–5615. doi: 10.1073/pnas.79.18.5611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gauwerky C. E., Haluska F. G., Tsujimoto Y., Nowell P. C., Croce C. M. Evolution of B-cell malignancy: pre-B-cell leukemia resulting from MYC activation in a B-cell neoplasm with a rearranged BCL2 gene. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8548–8552. doi: 10.1073/pnas.85.22.8548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gauwerky C. E., Hoxie J., Nowell P. C., Croce C. M. Pre-B-cell leukemia with a t(8; 14) and a t(14; 18) translocation is preceded by follicular lymphoma. Oncogene. 1988 May;2(5):431–435. [PubMed] [Google Scholar]
  10. Gidoni D., Dynan W. S., Tjian R. Multiple specific contacts between a mammalian transcription factor and its cognate promoters. 1984 Nov 29-Dec 5Nature. 312(5993):409–413. doi: 10.1038/312409a0. [DOI] [PubMed] [Google Scholar]
  11. Harper M. E., Saunders G. F. Localization of single copy DNA sequences of G-banded human chromosomes by in situ hybridization. Chromosoma. 1981;83(3):431–439. doi: 10.1007/BF00327364. [DOI] [PubMed] [Google Scholar]
  12. Huebner K., Cannizzaro L. A., Nakamura T., Hillova J., Mariage-Samson R., Hecht F., Hill M., Croce C. M. A rearranged transforming gene, tre, is made up of human sequences derived from chromosome regions 5q, 17q and 18q. Oncogene. 1988 Oct;3(4):449–455. [PubMed] [Google Scholar]
  13. Huebner K., Isobe M., Chao M., Bothwell M., Ross A. H., Finan J., Hoxie J. A., Sehgal A., Buck C. R., Lanahan A. The nerve growth factor receptor gene is at human chromosome region 17q12-17q22, distal to the chromosome 17 breakpoint in acute leukemias. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1403–1407. doi: 10.1073/pnas.83.5.1403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Leder A., Pattengale P. K., Kuo A., Stewart T. A., Leder P. Consequences of widespread deregulation of the c-myc gene in transgenic mice: multiple neoplasms and normal development. Cell. 1986 May 23;45(4):485–495. doi: 10.1016/0092-8674(86)90280-1. [DOI] [PubMed] [Google Scholar]
  15. Levine E. G., Arthur D. C., Frizzera G., Peterson B. A., Hurd D. D., Bloomfield C. D. Cytogenetic abnormalities predict clinical outcome in non-Hodgkin lymphoma. Ann Intern Med. 1988 Jan;108(1):14–20. doi: 10.7326/0003-4819-108-1-14. [DOI] [PubMed] [Google Scholar]
  16. Nowell P. C. The clonal evolution of tumor cell populations. Science. 1976 Oct 1;194(4260):23–28. doi: 10.1126/science.959840. [DOI] [PubMed] [Google Scholar]
  17. Payvar F., DeFranco D., Firestone G. L., Edgar B., Wrange O., Okret S., Gustafsson J. A., Yamamoto K. R. Sequence-specific binding of glucocorticoid receptor to MTV DNA at sites within and upstream of the transcribed region. Cell. 1983 Dec;35(2 Pt 1):381–392. doi: 10.1016/0092-8674(83)90171-x. [DOI] [PubMed] [Google Scholar]
  18. Pegoraro L., Palumbo A., Erikson J., Falda M., Giovanazzo B., Emanuel B. S., Rovera G., Nowell P. C., Croce C. M. A 14;18 and an 8;14 chromosome translocation in a cell line derived from an acute B-cell leukemia. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7166–7170. doi: 10.1073/pnas.81.22.7166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pelicci P. G., Knowles D. M., 2nd, Magrath I., Dalla-Favera R. Chromosomal breakpoints and structural alterations of the c-myc locus differ in endemic and sporadic forms of Burkitt lymphoma. Proc Natl Acad Sci U S A. 1986 May;83(9):2984–2988. doi: 10.1073/pnas.83.9.2984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Reed J. C., Cuddy M., Slabiak T., Croce C. M., Nowell P. C. Oncogenic potential of bcl-2 demonstrated by gene transfer. Nature. 1988 Nov 17;336(6196):259–261. doi: 10.1038/336259a0. [DOI] [PubMed] [Google Scholar]
  21. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schüle R., Muller M., Kaltschmidt C., Renkawitz R. Many transcription factors interact synergistically with steroid receptors. Science. 1988 Dec 9;242(4884):1418–1420. doi: 10.1126/science.3201230. [DOI] [PubMed] [Google Scholar]
  23. Showe L. C., Ballantine M., Nishikura K., Erikson J., Kaji H., Croce C. M. Cloning and sequencing of a c-myc oncogene in a Burkitt's lymphoma cell line that is translocated to a germ line alpha switch region. Mol Cell Biol. 1985 Mar;5(3):501–509. doi: 10.1128/mcb.5.3.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Tsai-Pflugfelder M., Liu L. F., Liu A. A., Tewey K. M., Whang-Peng J., Knutsen T., Huebner K., Croce C. M., Wang J. C. Cloning and sequencing of cDNA encoding human DNA topoisomerase II and localization of the gene to chromosome region 17q21-22. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7177–7181. doi: 10.1073/pnas.85.19.7177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tsujimoto Y., Cossman J., Jaffe E., Croce C. M. Involvement of the bcl-2 gene in human follicular lymphoma. Science. 1985 Jun 21;228(4706):1440–1443. doi: 10.1126/science.3874430. [DOI] [PubMed] [Google Scholar]
  26. Tsujimoto Y., Finger L. R., Yunis J., Nowell P. C., Croce C. M. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science. 1984 Nov 30;226(4678):1097–1099. doi: 10.1126/science.6093263. [DOI] [PubMed] [Google Scholar]
  27. Tsujimoto Y., Gorham J., Cossman J., Jaffe E., Croce C. M. The t(14;18) chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining. Science. 1985 Sep 27;229(4720):1390–1393. doi: 10.1126/science.3929382. [DOI] [PubMed] [Google Scholar]
  28. Vogelstein B., Fearon E. R., Hamilton S. R., Kern S. E., Preisinger A. C., Leppert M., Nakamura Y., White R., Smits A. M., Bos J. L. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988 Sep 1;319(9):525–532. doi: 10.1056/NEJM198809013190901. [DOI] [PubMed] [Google Scholar]
  29. ar-Rushdi A., Nishikura K., Erikson J., Watt R., Rovera G., Croce C. M. Differential expression of the translocated and the untranslocated c-myc oncogene in Burkitt lymphoma. Science. 1983 Oct 28;222(4622):390–393. doi: 10.1126/science.6414084. [DOI] [PubMed] [Google Scholar]

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