Fusion of the TEL Gene on 12p13 to the AML1 Gene on 21q22 in Acute Lymphoblastic Leukemia

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1995 May 23

PMID 7761424

Citations 158

Authors

T R Golub

G F Barker

S K Bohlander

S W Hiebert

D C Ward

E Morgan

S C Raimondi

J D Rowley

D G Gilliland

Affiliations

Soon will be listed here.

Abstract

Chromosomal rearrangements involving band 12p13 are found in a wide variety of human leukemias but are particularly common in childhood acute lymphoblastic leukemia. The genes involved in these rearrangements, however, have not been identified. We now report the cloning of a t(12;21) translocation breakpoint involving 12p13 and 21q22 in two cases of childhood pre-B acute lymphoblastic leukemia, in which t(12;21) rearrangements were not initially apparent. The consequence of the translocation is fusion of the helix-loop-helix domain of TEL, an ETS-like putative transcription factor, to the DNA-binding and transactivation domains of the transcription factor AML1. These data show that TEL, previously shown to be fused to the platelet-derived growth factor receptor beta in chronic myelomonocytic leukemia, can be implicated in the pathogenesis of leukemia through its fusion to either a receptor tyrosine kinase or a transcription factor. The TEL-AML1 fusion also indicates that translocations affecting the AML1 gene can be associated with lymphoid, as well as myeloid, malignancy.

Citing Articles

The Diverse Roles of ETV6 Alterations in B-Lymphoblastic Leukemia and Other Hematopoietic Cancers.

Monovich A, Gurumurthy A, Ryan R Adv Exp Med Biol. 2024; 1459:291-320.

PMID: 39017849 DOI: 10.1007/978-3-031-62731-6_13.

Generation of a Zebrafish Knock-In Model Recapitulating Childhood ETV6::RUNX1-Positive B-Cell Precursor Acute Lymphoblastic Leukemia.

Zapilko V, Moisio S, Parikka M, Heinaniemi M, Lohi O Cancers (Basel). 2023; 15(24).

PMID: 38136366 PMC: 10871125. DOI: 10.3390/cancers15245821.

Sticky, Adaptable, and Many-sided: SAM protein versatility in normal and pathological hematopoietic states.

Ray S, Hewitt K Bioessays. 2023; 45(8):e2300022.

PMID: 37318311 PMC: 10527593. DOI: 10.1002/bies.202300022.

The Landscape of Secondary Genetic Rearrangements in Pediatric Patients with B-Cell Acute Lymphoblastic Leukemia with t(12;21).

Kaczmarska A, Derebas J, Pinkosz M, Niedzwiecki M, Lejman M Cells. 2023; 12(3).

PMID: 36766699 PMC: 9913634. DOI: 10.3390/cells12030357.

The ETS transcription factor ETV6 constrains the transcriptional activity of EWS-FLI to promote Ewing sarcoma.

Lu D, Ellegast J, Ross K, Malone C, Lin S, Mabe N Nat Cell Biol. 2023; 25(2):285-297.

PMID: 36658220 PMC: 9928584. DOI: 10.1038/s41556-022-01059-8.

References

Birren B, Lai E, Hood L, Simon M . Pulsed field gel electrophoresis techniques for separating 1- to 50-kilobase DNA fragments. Anal Biochem. 1989; 177(2):282-6. DOI: 10.1016/0003-2697(89)90052-3. View

Kobayashi H, Rowley J . Identification of cytogenetically undetected 12p13 translocations and associated deletions with fluorescence in situ hybridization. Genes Chromosomes Cancer. 1995; 12(1):66-9. DOI: 10.1002/gcc.2870120112. View

Erickson P, Gao J, Chang K, Look T, Whisenant E, Raimondi S . Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript, AML1/ETO, with similarity to Drosophila segmentation gene, runt. Blood. 1992; 80(7):1825-31. View

Nisson P, Watkins P, Sacchi N . Transcriptionally active chimeric gene derived from the fusion of the AML1 gene and a novel gene on chromosome 8 in t(8;21) leukemic cells. Cancer Genet Cytogenet. 1992; 63(2):81-8. DOI: 10.1016/0165-4608(92)90384-k. View

Wasylyk B, Hahn S, Giovane A . The Ets family of transcription factors. Eur J Biochem. 1993; 211(1-2):7-18. DOI: 10.1007/978-3-642-78757-7_2. View

Raimondi S . Current status of cytogenetic research in childhood acute lymphoblastic leukemia. Blood. 1993; 81(9):2237-51. View

Frohman M . Rapid amplification of complementary DNA ends for generation of full-length complementary DNAs: thermal RACE. Methods Enzymol. 1993; 218:340-56. DOI: 10.1016/0076-6879(93)18026-9. View

Ogawa E, Maruyama M, Kagoshima H, Inuzuka M, Lu J, Satake M . PEBP2/PEA2 represents a family of transcription factors homologous to the products of the Drosophila runt gene and the human AML1 gene. Proc Natl Acad Sci U S A. 1993; 90(14):6859-63. PMC: 47032. DOI: 10.1073/pnas.90.14.6859. View

Liu P, Tarle S, Hajra A, Claxton D, Marlton P, Freedman M . Fusion between transcription factor CBF beta/PEBP2 beta and a myosin heavy chain in acute myeloid leukemia. Science. 1993; 261(5124):1041-4. DOI: 10.1126/science.8351518. View

10.

Nucifora G, Begy C, Erickson P, Drabkin H, Rowley J . The 3;21 translocation in myelodysplasia results in a fusion transcript between the AML1 gene and the gene for EAP, a highly conserved protein associated with the Epstein-Barr virus small RNA EBER 1. Proc Natl Acad Sci U S A. 1993; 90(16):7784-8. PMC: 47227. DOI: 10.1073/pnas.90.16.7784. View

11.

Mitani K, Ogawa S, Tanaka T, Miyoshi H, Kurokawa M, Mano H . Generation of the AML1-EVI-1 fusion gene in the t(3;21)(q26;q22) causes blastic crisis in chronic myelocytic leukemia. EMBO J. 1994; 13(3):504-10. PMC: 394839. DOI: 10.1002/j.1460-2075.1994.tb06288.x. View

12.

Johansson B, Mertens F, Mitelman F . Cytogenetic deletion maps of hematologic neoplasms: circumstantial evidence for tumor suppressor loci. Genes Chromosomes Cancer. 1993; 8(4):205-18. DOI: 10.1002/gcc.2870080402. View

13.

Golub T, Barker G, Lovett M, Gilliland D . Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation. Cell. 1994; 77(2):307-16. DOI: 10.1016/0092-8674(94)90322-0. View

14.

Nucifora G, Begy C, Kobayashi H, Roulston D, Claxton D, Pedersen-Bjergaard J . Consistent intergenic splicing and production of multiple transcripts between AML1 at 21q22 and unrelated genes at 3q26 in (3;21)(q26;q22) translocations. Proc Natl Acad Sci U S A. 1994; 91(9):4004-8. PMC: 43711. DOI: 10.1073/pnas.91.9.4004. View

15.

Romana S, Le Coniat M, Berger R . t(12;21): a new recurrent translocation in acute lymphoblastic leukemia. Genes Chromosomes Cancer. 1994; 9(3):186-91. DOI: 10.1002/gcc.2870090307. View

16.

Kobayashi H, Montgomery K, Bohlander S, Adra C, Lim B, Kucherlapati R . Fluorescence in situ hybridization mapping of translocations and deletions involving the short arm of human chromosome 12 in malignant hematologic diseases. Blood. 1994; 84(10):3473-82. View

17.

Levanon D, NEGREANU V, Bernstein Y, Bar-Am I, Avivi L, Groner Y . AML1, AML2, and AML3, the human members of the runt domain gene-family: cDNA structure, expression, and chromosomal localization. Genomics. 1994; 23(2):425-32. DOI: 10.1006/geno.1994.1519. View

18.

Miyoshi H, Shimizu K, Kozu T, Maseki N, Kaneko Y, Ohki M . t(8;21) breakpoints on chromosome 21 in acute myeloid leukemia are clustered within a limited region of a single gene, AML1. Proc Natl Acad Sci U S A. 1991; 88(23):10431-4. PMC: 52942. DOI: 10.1073/pnas.88.23.10431. View