Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
September-2014 Volume 8 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
September-2014 Volume 8 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review

NUP214 fusion genes in acute leukemia (Review)

  • Authors:
    • Min‑Hang Zhou
    • Qing‑Ming Yang
  • View Affiliations / Copyright

    Affiliations: Department of Hematology and Oncology, The First Affiliated Hospital of the People's Liberation Army General Hospital, Beijing 100048, P.R. China
  • Pages: 959-962
    |
    Published online on: June 18, 2014
       https://doi.org/10.3892/ol.2014.2263
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Nucleoporin 214 (NUP214), previously termed CAN, is required for cell cycle and nucleocytoplasmic transport. The genetic features and clinical implications of five NUP214‑associated fusion genes are described in this review. SET‑NUP214 was most frequently observed in T‑cell acute lymphoblastic leukemia (T‑ALL), concomitant with the elevated expression of HOXA cluster genes. Furthermore, the fusion transcript may be regarded as a potential minimal residual disease marker for SET‑NUP214‑positive patients. Episomal amplifications of NUP214‑ABL1 are specific to T‑ALL patients. The NUP214‑ABL1 gene is observed in ~6% of T‑ALL, in children and adults. Targeted tyrosine kinase inhibitors plus standard chemotherapy appear to present a promising treatment strategy. DEK‑NUP214 is formed by the fusion of exon 2 of DEK and exon 6 of NUP214. Achieving molecular negativity of DEK‑NUP214 is of great importance for individual management. SQSTM1‑NUP214 and NUP214‑XKR3 were only identified in one T‑ALL patient and one cell line, respectively. The NUP214 fusions have significant diagnostic and therapeutic implications for leukemia patients. Additional NUP214‑associated fusions require identification in future studies.
View Figures
View References

1 

Kraemer D, Wozniak RW, Blobel G and Radu A: The human CAN protein, a putative oncogene product associated with myeloid leukemogenesis, is a nuclear pore complex protein that faces the cytoplasm. Proc Natl Acad Sci USA. 91:1519–1523. 1994.

2 

Fan Z, Beresford PJ, Oh DY, Zhang D and Lieberman J: Tumor suppressor NM23-H1 is a granzyme A-activated DNase during CTL-mediated apoptosis, and the nucleosome assembly protein SET is its inhibitor. Cell. 112:659–672. 2003.

3 

Quentmeier H, Schneider B, Röhrs S, et al: SET-NUP214 fusion in acute myeloid leukemia- and T-cell acute lymphoblastic leukemia-derived cell lines. J Hematol Oncol. 2:32009.

4 

Gorello P, La Starza R, Varasano E, et al: Combined interphase fluorescence in situ hybridization elucidates the genetic heterogeneity of T-cell acute lymphoblastic leukemia in adults. Haematologica. 95:79–86. 2010.

5 

Chae H, Lim J, Kim M, et al: Phenotypic and genetic characterization of adult T-cell acute lymphoblastic leukemia with del(9)(q34);SET-NUP214 rearrangement. Ann Hematol. 91:193–201. 2012.

6 

Van Vlierberghe P, van Grotel M, Tchinda J, et al: The recurrent SET-NUP214 fusion as a new HOXA activation mechanism in pediatric T-cell acute lymphoblastic leukemia. Blood. 111:4668–4680. 2008.

7 

Rosati R, La Starza R, Barba G, et al: Cryptic chromosome 9q34 deletion generates TAF-Ialpha/CAN and TAF-Ibeta/CAN fusion transcripts in acute myeloid leukemia. Haematologica. 92:232–235. 2007.

8 

von Lindern M, Breems D, van Baal S, Adriaansen H and Grosveld G: Characterization of the translocation breakpoint sequences of two DEK-CAN fusion genes present in t(6;9) acute myeloid leukemia and a SET-CAN fusion gene found in a case of acute undifferentiated leukemia. Genes Chromosomes Cancer. 5:227–234. 1992.

9 

Okada Y, Jiang Q, Lemieux M, Jeannotte L, Su L and Zhang Y: Leukaemic transformation by CALM-AF10 involves upregulation of Hoxa5 by hDOT1L. Nat Cell Biol. 8:1017–1024. 2006.

10 

Speleman F, Cauwelier B, Dastugue N, et al: A new recurrent inversion, inv(7)(p15q34), leads to transcriptional activation of HOXA10 and HOXA11 in a subset of T-cell acute lymphoblastic leukemias. Leukemia. 19:358–366. 2005.

11 

Ferrando AA, Armstrong SA, Neuberg DS, et al: Gene expression signatures in MLL-rearranged T-lineage and B-precursor acute leukemias: dominance of HOX dysregulation. Blood. 102:262–268. 2003.

12 

Kandilci A, Mientjes E and Grosveld G: Effects of SET and SET-CAN on the differentiation of the human promonocytic cell line U937. Leukemia. 18:337–340. 2004.

13 

Saito S, Nouno K, Shimizu R, Yamamoto M and Nagata K: Impairment of erythroid and megakaryocytic differentiation by a leukemia-associated and t(9;9)-derived fusion gene product, SET/TAF-Ibeta-CAN/Nup214. J Cell Physiol. 214:322–333. 2008.

14 

De Keersmaecker K, Marynen P and Cools J: Genetic insights in the pathogenesis of T-cell acute lymphoblastic leukemia. Haematologica. 90:1116–1127. 2005.

15 

Liu F, Gao L, Jing Y, et al: Detection and clinical significance of gene rearrangements in Chinese patients with adult acute lymphoblastic leukemia. Leuk Lymphoma. 54:1521–1526. 2013.

16 

Wang Q, Qiu H, Jiang H, et al: Mutations of PHF6 are associated with mutations of NOTCH1, JAK1 and rearrangement of SET-NUP214 in T-cell acute lymphoblastic leukemia. Haematologica. 96:1808–1814. 2011.

17 

Weng AP, Ferrando AA, Lee W, et al: Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science. 306:269–271. 2004.

18 

Li WJ, Cui L, Gao C, et al: MRD analysis and treatment outcome in three children with SET-NUP214-positive hematological malignancies. Int J Lab Hematol. 33:e25–e27. 2011.

19 

de Klein A, van Kessel AG, Grosveld G, et al: A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia. Nature. 300:765–767. 1982.

20 

De Braekeleer E, Douet-Guilbert N, Rowe D, et al: ABL1 fusion genes in hematological malignancies: a review. Eur J Haematol. 86:361–371. 2011.

21 

De Keersmaecker K, Rocnik JL, Bernad R, et al: Kinase activation and transformation by NUP214-ABL1 is dependent on the context of the nuclear pore. Mol Cell. 31:134–142. 2008.

22 

Maurer BJ, Lai E, Hamkalo BA, Hood L and Attardi G: Novel submicroscopic extrachromosomal elements containing amplified genes in human cells. Nature. 327:434–437. 1987.

23 

Carroll SM, DeRose ML, Gaudray P, et al: Double minute chromosomes can be produced from precursors derived from a chromosomal deletion. Mol Cell Biol. 8:1525–1533. 1988.

24 

Graux C, Stevens-Kroef M, Lafage M, et al: Groupe Francophone de Cytogénétique Hématologique; Belgian Cytogenetic Group for Hematology and Oncology: Heterogeneous patterns of amplification of the NUP214-ABL1 fusion gene in T-cell acute lymphoblastic leukemia. Leukemia. 23:125–133. 2009.

25 

Eyre T, Schwab CJ, Kinstrie R, et al: Episomal amplification of NUP214-ABL1 fusion gene in B-cell acute lymphoblastic leukemia. Blood. 120:4441–4443. 2012.

26 

Roberts KG, Morin RD, Zhang J, et al: Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia. Cancer Cell. 22:153–166. 2012.

27 

Burmeister T, Gökbuget N, Reinhardt R, Rieder H, Hoelzer D and Schwartz S: NUP214-ABL1 in adult T-ALL: the GMALL study group experience. Blood. 108:3556–3559. 2006.

28 

Ballerini P, Landman-Parker J, Cayuela JM, et al: Impact of genotype on survival of children with T-cell acute lymphoblastic leukemia treated according to the French protocol FRALLE-93: the effect of TLX3/HOX11L2 gene expression on outcome. Haematologica. 93:1658–1665. 2008.

29 

Ballerini P, Busson M, Fasola S, et al: NUP214-ABL1 amplification in t(5;14)/HOX11L2-positive ALL present with several forms and may have a prognostic significance. Leukemia. 19:468–470. 2005.

30 

Graux C, Cools J, Melotte C, et al: Fusion of NUP214 to ABL1 on amplified episomes in T-cell acute lymphoblastic leukemia. Nat Genet. 36:1084–1089. 2004.

31 

Hagemeijer A and Graux C: ABL1 rearrangements in T-cell acute lymphoblastic leukemia. Genes Chromosomes Cancer. 49:299–308. 2010.

32 

Quintás-Cardama A, Tong W, Manshouri T, et al: Activity of tyrosine kinase inhibitors against human NUP214-ABL1-positive T cell malignancies. Leukemia. 22:1117–1124. 2008.

33 

Druker BJ: Translation of the Philadelphia chromosome into therapy for CML. Blood. 112:4808–4817. 2008.

34 

Kleppe M, Lahortiga I, El Chaar T, et al: Deletion of the protein tyrosine phosphatase gene PTPN2 in T-cell acute lymphoblastic leukemia. Nat Genet. 42:530–535. 2010.

35 

Clarke S, O’Reilly J, Romeo G and Cooney J: NUP214-ABL1 positive T-cell acute lymphoblastic leukemia patient shows an initial favorable response to imatinib therapy post relapse. Leuk Res. 35:e131–e133. 2011.

36 

De Keersmaecker K, Porcu M, Cox L, et al: NUP214-ABL1 mediated cell proliferation in T-cell acute lymphoblastic leukemia is dependent on the LCK kinase and various interacting proteins. Haematologica. 99:85–93. 2013.

37 

De Keersmaecker K, Versele M, Cools J, Superti-Furga G and Hantschel O: Intrinsic differences between the catalytic properties of the oncogenic NUP214-ABL1 and BCR-ABL1 fusion protein kinases. Leukemia. 22:2208–2216. 2008.

38 

Deenik W, Beverloo HB, van der Poel-van de Luytgaarde SC, et al: Rapid complete cytogenetic remission after upfront dasatinib monotherapy in a patient with a NUP214-ABL1-positive T-cell acute lymphoblastic leukemia. Leukemia. 23:627–629. 2009.

39 

Slovak ML, Gundacker H, Bloomfield CD, et al: A retrospective study of 69 patients with t(6;9)(p23;q34) AML emphasizes the need for a prospective, multicenter initiative for rare ‘poor prognosis’ myeloid malignancies. Leukemia. 20:1295–1297. 2006.

40 

Cho YU, Chi HS, Park CJ, Jang S and Seo EJ: Rapid detection of prognostically significant fusion transcripts in acute leukemia using simplified multiplex reverse transcription polymerase chain reaction. J Korean Med Sci. 27:1155–1161. 2012.

41 

Sandén C, Ageberg M, Petersson J, Lennartsson A and Gullberg U: Forced expression of the DEK-NUP214 fusion protein promotes proliferation dependent on upregulation of mTOR. BMC Cancer. 13:4402013.

42 

von Lindern M, Fornerod M, van Baal S, et al: The translocation (6;9), associated with a specific subtype of acute myeloid leukemia, results in the fusion of two genes, dek and can, and the expression of a chimeric, leukemia-specific dek-can mRNA. Mol Cell Biol. 12:1687–1697. 1992.

43 

Rowley JD: Recurring chromosome abnormalities in leukemia and lymphoma. Semin Hematol. 27:122–136. 1990.

44 

Chi Y, Lindgren V, Quigley S and Gaitonde S: Acute myelogenous leukemia with t(6;9)(p23;q34) and marrow basophilia: an overview. Arch Pathol Lab Med. 132:1835–1837. 2008.

45 

Thiede C, Steudel C, Mohr B, et al: Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood. 99:4326–4335. 2002.

46 

Garçon L, Libura M, Delabesse E, et al: DEK-CAN molecular monitoring of myeloid malignancies could aid therapeutic stratification. Leukemia. 19:1338–1344. 2005.

47 

Pursiheimo JP, Rantanen K, Heikkinen PT, Johansen T and Jaakkola PM: Hypoxia-activated autophagy accelerates degradation of SQSTM1/p62. Oncogene. 28:334–344. 2009.

48 

Gorello P, La Starza R, Di Giacomo D, et al: SQSTM1-NUP214: a new gene fusion in adult T-cell acute lymphoblastic leukemia. Haematologica. 95:2161–2163. 2010.

49 

Saito S, Miyaji-Yamaguchi M and Nagata K: Aberrant intracellular localization of SET-CAN fusion protein, associated with a leukemia, disorganizes nuclear export. Int J Cancer. 111:501–507. 2004.

50 

Fornerod M, Boer J, van Baal S, Morreau H and Grosveld G: Interaction of cellular proteins with the leukemia specific fusion proteins DEK-CAN and SET-CAN and their normal counterpart, the nucleoporin CAN. Oncogene. 13:1801–1808. 1996.

51 

Calenda G, Peng J, Redman CM, Sha Q, Wu X and Lee S: Identification of two new members, XPLAC and XTES, of the XK family. Gene. 370:6–16. 2006.

52 

Levin JZ, Berger MF, Adiconis X, et al: Targeted next-generation sequencing of a cancer transcriptome enhances detection of sequence variants and novel fusion transcripts. Genome Biol. 10:R1152009.

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhou MH and Yang QM: NUP214 fusion genes in acute leukemia (Review). Oncol Lett 8: 959-962, 2014.
APA
Zhou, M., & Yang, Q. (2014). NUP214 fusion genes in acute leukemia (Review). Oncology Letters, 8, 959-962. https://doi.org/10.3892/ol.2014.2263
MLA
Zhou, M., Yang, Q."NUP214 fusion genes in acute leukemia (Review)". Oncology Letters 8.3 (2014): 959-962.
Chicago
Zhou, M., Yang, Q."NUP214 fusion genes in acute leukemia (Review)". Oncology Letters 8, no. 3 (2014): 959-962. https://doi.org/10.3892/ol.2014.2263
Copy and paste a formatted citation
x
Spandidos Publications style
Zhou MH and Yang QM: NUP214 fusion genes in acute leukemia (Review). Oncol Lett 8: 959-962, 2014.
APA
Zhou, M., & Yang, Q. (2014). NUP214 fusion genes in acute leukemia (Review). Oncology Letters, 8, 959-962. https://doi.org/10.3892/ol.2014.2263
MLA
Zhou, M., Yang, Q."NUP214 fusion genes in acute leukemia (Review)". Oncology Letters 8.3 (2014): 959-962.
Chicago
Zhou, M., Yang, Q."NUP214 fusion genes in acute leukemia (Review)". Oncology Letters 8, no. 3 (2014): 959-962. https://doi.org/10.3892/ol.2014.2263
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team