Acute myeloid leukaemia with DEK::NUP214 fusion

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N/Haematolymphoid Tumours (WHO Classification, 5th ed.)

editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification
This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Acute Myeloid Leukemia (AML) with t(6;9)(p23;q34.1); DEK-NUP214.

Primary Author(s)*

Jennelle C. Hodge, PhD, FACMG

WHO Classification of Disease

Structure Disease
Book Haematolymphoid Tumours (5th ed.)
Category Myeloid proliferations and neoplasms
Family Acute myeloid leukaemia
Type Acute myeloid leukaemia with defining genetic abnormalities
Subtype(s) Acute myeloid leukaemia with DEK::NUP214 fusion

WHO Essential and Desirable Genetic Diagnostic Criteria

WHO Essential Criteria (Genetics)* Presence of DEK::NUP214 fusion
WHO Desirable Criteria (Genetics)* Detection of t(6;9)(p22.3;q34.1)
Other Classification N/A

*Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the WHO Classification of Tumours.

Related Terminology

Acceptable
Not Recommended

Gene Rearrangements

T(6;9)(p23;q34).png

This AML subtype is classified based on the presence of a t(6;9)(p23;q34.1), which results in fusion of the 5’ portion of DEK at “6p23” (specifically 6p22.3[hg38]) and the 3’ portion of NUP214(CAN) at “9q34.1” (specifically 9q34.13[hg38]). The breakpoints are intronic, producing an in-frame fusion[1]. The DEK-NUP214 fusion present on the derivative chromosome 6 is considered the pathogenic entity as the reciprocal NUP214-DEK fusion on chromosome 9 does not appear to be transcribed[2]. Typically, the DEK-NUP214 fusion presents as the sole abnormality but can be part of a complex karyotype[3]. Cases with the 6;9 translocation and <20% blasts are not currently classified as AML, which is controversial. Such cases should have close follow-up to monitor for development of more definitive evidence of AML or may be treated as AML if clinically appropriate[3].

Driver Gene Fusion(s) and Common Partner Genes Molecular Pathogenesis Typical Chromosomal Alteration(s) Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease) Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
DEK DEK::NUP214 The pathogenic derivative is the der(6) resulting in fusion of the proto-oncogene 5’ DEK and 3’NUP214(CAN). t(6;9)(p23;q34.1) Rare (AML) D, P Yes (WHO) The t(6;9) occurs in 0.6-1.7% of AML cases in children (REFERENCES) and about 1% of adult AML cases (REFERENCES). DEK::NUP214 has traditionally been associated with a poor prognosis in both adult and pediatric AML cases[3]. Of note, a 2014 retrospective analysis suggests a better outcome for pediatric patients with this translocation than previously reported[4]. Elevated white blood cell counts and higher bone marrow blast percentages are associated with shorter periods of overall survival and disease-free survival, respectively[3]. Limited data suggests early allogeneic stem cell transplantation may be associated with better overall survival compared to patients without transplantation, suggesting accurate diagnosis for these patients is crucial[3][5][6]. The concurrent presence of FLT3-ITD does not appear to negatively impact survival in the pediatric population[3].

Individual Region Genomic Gain/Loss/LOH

Chr # Gain, Loss, Amp, LOH Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size] Relevant Gene(s) Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
N/A

Characteristic Chromosomal or Other Global Mutational Patterns

Chromosomal Pattern Molecular Pathogenesis Prevalence -

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
N/A

Gene Mutations (SNV/INDEL)

COSMIC does not have specific information on mutations related to this subtype of AML.

Gene Genetic Alteration Tumor Suppressor Gene, Oncogene, Other Prevalence -

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

Diagnostic, Prognostic, and Therapeutic Significance - D, P, T   Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
FLT3


ITD mutations Oncogene Common (AML with DEK::NUP214 fusion) EXAMPLE: T EXAMPLE: Yes (NCCN) FLT3-ITD occurs in 69% of children and 78% of adults. In contrast to FLT3-ITD mutations, FLT3-TKD is very uncommon. The concurrent presence of FLT3-ITD with t(6;9) does not appear to negatively impact survival in the pediatric population[3].

Note: A more extensive list of mutations can be found in cBioportal, COSMIC, and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

Epigenomic Alterations

Not applicable

Genes and Main Pathways Involved

The molecular mechanism is not completely understood, but the fusion protein is known to act as an aberrant transcription factor, alter nuclear transport and induce myeloid cell-specific global protein synthesis[3][7].

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
N/A

Genetic Diagnostic Testing Methods

Karyotype, FISH, RT-PCR

Familial Forms

Not applicable

Additional Information

Not applicable

Links

DEK

NUP214

References

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  1. ↑ von Lindern, M.; et al. (1992). "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". Molecular and Cellular Biology. 12 (4): 1687–1697. doi:10.1128/mcb.12.4.1687. ISSN 0270-7306. PMC 369612. PMID 1549122.CS1 maint: PMC format (link)
  2. ↑ von Lindern, M.; et al. (1992). "Translocation t(6;9) in acute non-lymphocytic leukaemia results in the formation of a DEK-CAN fusion gene". Bailliere's Clinical Haematology. 5 (4): 857–879. doi:10.1016/s0950-3536(11)80049-1. ISSN 0950-3536. PMID 1308167.
  3. ↑ Jump up to: 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p137-138.
  4. ↑ Sandahl, Julie Damgaard; et al. (2014). "t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients". Haematologica. 99 (5): 865–872. doi:10.3324/haematol.2013.098517. ISSN 1592-8721. PMC 4008104. PMID 24441146.
  5. ↑ Slovak, M. L.; et al. (2006). "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 (7): 1295–1297. doi:10.1038/sj.leu.2404233. ISSN 0887-6924. PMID 16628187.
  6. ↑ Ishiyama, K.; et al. (2012). "Allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with t(6;9)(p23;q34) dramatically improves the patient prognosis: a matched-pair analysis". Leukemia. 26 (3): 461–464. doi:10.1038/leu.2011.229. ISSN 1476-5551. PMID 21869835.
  7. ↑ Ageberg, Malin; et al. (2008). "Identification of a novel and myeloid specific role of the leukemia-associated fusion protein DEK-NUP214 leading to increased protein synthesis". Genes, Chromosomes & Cancer. 47 (4): 276–287. doi:10.1002/gcc.20531. ISSN 1098-2264. PMID 18181180.


Notes

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Prior Author(s):


*Citation of this Page: “Acute myeloid leukaemia with DEK::NUP214 fusion”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 05/10/2025, https://ccga.io/index.php/HAEM5:Acute_myeloid_leukaemia_with_DEK::NUP214_fusion.

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