Activation of MYC in a Masked T(8;17) Translocation Results in an Aggressive B-cell Leukemia

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1989 Nov 1

PMID 2682663

Citations 31

Authors

C E Gauwerky

K Huebner

M Isobe

P C Nowell

C M Croce

Affiliations

Soon will be listed here.

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.

Citing Articles

MicroRNAs: where brilliance, perseverance, and ambition converged.

Drula R, Calin G J Clin Invest. 2024; 135(2).

PMID: 39656547 PMC: 11735086. DOI: 10.1172/JCI189625.

Multifaceted roles for BCL3 in cancer: a proto-oncogene comes of age.

Seaton G, Smith H, Brancale A, Westwell A, Clarkson R Mol Cancer. 2024; 23(1):7.

PMID: 38195591 PMC: 10775530. DOI: 10.1186/s12943-023-01922-8.

Exploring the Relationship between Fusion Genes and MicroRNAs in Cancer.

Panicker S, Chengizkhan G, Gor R, Ramachandran I, Ramalingam S Cells. 2023; 12(20).

PMID: 37887311 PMC: 10605240. DOI: 10.3390/cells12202467.

Changes of Protein Expression after CRISPR/Cas9 Knockout of miRNA-142 in Cell Lines Derived from Diffuse Large B-Cell Lymphoma.

Menegatti J, Nakel J, Stepanov Y, Caban K, Ludwig N, Nord R Cancers (Basel). 2022; 14(20).

PMID: 36291816 PMC: 9600116. DOI: 10.3390/cancers14205031.

MiRNA-142-3P and FUS can be Sponged by Long Noncoding RNA to Promote Cell Proliferation in Acute Myeloid Leukemia.

Yin Z, Shen H, Gu C, Zhang M, Liu Z, Huang J Front Mol Biosci. 2021; 8:754936.

PMID: 34746238 PMC: 8570042. DOI: 10.3389/fmolb.2021.754936.

References

Nowell P . The clonal evolution of tumor cell populations. Science. 1976; 194(4260):23-8. DOI: 10.1126/science.959840. View

Huebner K, Cannizzaro L, Nakamura T, Hillova J, Hecht F, Hill M . A rearranged transforming gene, tre, is made up of human sequences derived from chromosome regions 5q, 17q and 18q. Oncogene. 1988; 3(4):449-55. View

Chirgwin J, Przybyla A, MacDonald R, Rutter W . Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979; 18(24):5294-9. DOI: 10.1021/bi00591a005. View

Harper M, Saunders G . Localization of single copy DNA sequences of G-banded human chromosomes by in situ hybridization. Chromosoma. 1981; 83(3):431-9. DOI: 10.1007/BF00327364. View

Erikson J, Finan J, Nowell P, Croce C . Translocation of immunoglobulin VH genes in Burkitt lymphoma. Proc Natl Acad Sci U S A. 1982; 79(18):5611-5. PMC: 346954. DOI: 10.1073/pnas.79.18.5611. View

Dierks P, Ooyen A, Cochran M, 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; 32(3):695-706. DOI: 10.1016/0092-8674(83)90055-7. View

Nishikura K, Erikson J, Watt R, Rovera G, Croce C . Differential expression of the translocated and the untranslocated c-myc oncogene in Burkitt lymphoma. Science. 1983; 222(4622):390-3. DOI: 10.1126/science.6414084. View

Payvar F, DeFranco D, Firestone G, Edgar B, Wrange O, Okret S . Sequence-specific binding of glucocorticoid receptor to MTV DNA at sites within and upstream of the transcribed region. Cell. 1983; 35(2 Pt 1):381-92. DOI: 10.1016/0092-8674(83)90171-x. View

Dayton A, Selden J, Laws G, Dorney D, Finan J, Tripputi P . 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; 81(14):4495-9. PMC: 345617. DOI: 10.1073/pnas.81.14.4495. View

10.

Tsujimoto Y, Finger L, Yunis J, Nowell P, Croce C . Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science. 1984; 226(4678):1097-9. DOI: 10.1126/science.6093263. View

11.

Gidoni D, Dynan W, Tjian R . Multiple specific contacts between a mammalian transcription factor and its cognate promoters. Nature. 1984; 312(5993):409-13. DOI: 10.1038/312409a0. View

12.

Pegoraro L, Palumbo A, Erikson J, Falda M, Giovanazzo B, Emanuel B . 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; 81(22):7166-70. PMC: 392098. DOI: 10.1073/pnas.81.22.7166. View

13.

Showe L, Ballantine M, Nishikura K, Erikson J, Kaji H, Croce C . 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; 5(3):501-9. PMC: 366742. DOI: 10.1128/mcb.5.3.501-509.1985. View

14.

Tsujimoto Y, Cossman J, Jaffe E, Croce C . Involvement of the bcl-2 gene in human follicular lymphoma. Science. 1985; 228(4706):1440-3. DOI: 10.1126/science.3874430. View

15.

Tsujimoto Y, Gorham J, Cossman J, Jaffe E, Croce C . The t(14;18) chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining. Science. 1985; 229(4720):1390-3. DOI: 10.1126/science.3929382. View

16.

Huebner K, Isobe M, Chao M, Bothwell M, Ross A, Finan J . 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; 83(5):1403-7. PMC: 323084. DOI: 10.1073/pnas.83.5.1403. View

17.

Pelicci P, Knowles 2nd D, 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; 83(9):2984-8. PMC: 323431. DOI: 10.1073/pnas.83.9.2984. View

18.

Leder A, Pattengale P, Kuo A, Stewart T, Leder P . Consequences of widespread deregulation of the c-myc gene in transgenic mice: multiple neoplasms and normal development. Cell. 1986; 45(4):485-95. DOI: 10.1016/0092-8674(86)90280-1. View

19.

Coussens L, Parker P, Rhee L, Yang-Feng T, Chen E, Waterfield M . Multiple, distinct forms of bovine and human protein kinase C suggest diversity in cellular signaling pathways. Science. 1986; 233(4766):859-66. DOI: 10.1126/science.3755548. View

20.

Croce C . Role of chromosome translocations in human neoplasia. Cell. 1987; 49(2):155-6. DOI: 10.1016/0092-8674(87)90552-6. View