HAEM5:Acute myeloid leukaemia with DEK::NUP214 fusion

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

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

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)	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. 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. Typically, the DEK-NUP214 fusion presents as the sole abnormality but can be part of a complex karyotype. 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. 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. Of note, a 2014 retrospective analysis suggests a better outcome for pediatric patients with this translocation than previously reported. Elevated white blood cell counts and higher bone marrow blast percentages are associated with shorter periods of overall survival and disease-free survival, respectively. 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. The concurrent presence of FLT3-ITD does not appear to negatively impact survival in the pediatric population.

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.

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

Gene; Genetic Alteration	Pathway	Pathophysiologic Outcome
DEK::NUP214	Unknown	The fusion protein is known to act as an aberrant transcription factor, alter nuclear transport and induce myeloid cell-specific global protein synthesis.

Genetic Diagnostic Testing Methods

Karyotype, FISH, RT-PCR

Familial Forms

Not applicable

Additional Information

Not applicable

Links

DEK

NUP214

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 05/17/2025, https://ccga.io/index.php/HAEM5:Acute_myeloid_leukaemia_with_DEK::NUP214_fusion.