Bone marrow neoplastic
Bone marrow - neoplastic myeloid
AML with recurrent genetic abnormalities
AML with t(6;9)(p23;q34); DEK::NUP214
Board of reviewers: Barina Aqil, M.D.
Deputy Editor-in-Chief: Genevieve M. Crane, M.D., Ph.D.
Last staff update: 27 March 2025 (update in progress)
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PubMed Search: AML with DEK::NUP214
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Pathophysiology | Etiology | Diagnosis | Laboratory | Prognostic factors | Case reports | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Peripheral smear description | Peripheral smear images | Flow cytometry description | Flow cytometry images | Molecular / cytogenetics description | Molecular / cytogenetics images | Videos | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1Cite this page: George GV, Burack WR. AML with t(6;9)(p23;q34); DEK::NUP214. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/leukemiaAMLt69.html. Accessed March 31st, 2025.
Definition / general
- Acute myeloid leukemia (AML) with DEK::NUP214 fusion is a genetically defined subtype of AML characterized by the fusion of the proto-oncogene DEK and the nucleoporin 214 gene (NUP214, formerly CAN) (Leukemia 2022;36:1703)
Essential features
- DEK::NUP214 fusion is AML defining irrespective of blast percentage (WHO5) but requires >=10% blasts in 2022 ICC
- Characteristically, this entity has a poor prognosis
- Multilineage dysplasia is present
- Basophilia is typically observed in this entity
Terminology
- AML with t(6;9)(p22.3;q34.1) (Leukemia 2022;36:1703)
- AML with DEK::NUP214 fusion
ICD coding
- ICD-10: C92.Z - other myeloid leukemia
Epidemiology
- This entity is rare, accounting for 0.6 - 1.7% of AML cases in children and 1% of AML cases in adults (Leukemia 2022;36:1703)
Pathophysiology
- DEK::NUP214 fusion may disrupt the localization of proteins essential for nucleocytoplasmic transport, possibly by inhibiting NFκB mediated transcription (Leukemia 2022;36:1703)
Etiology
- Unknown
Diagnosis
- Essential diagnostic criteria include (Leukemia 2022;36:1703)
- Diagnosis requires >=10% blasts criteria for ICC 2022 but the DEK::NUP214 fusion is AML defining irrespective of blast percentage according to WHO5
- Molecular or cytogenetic (FISH) detection of the DEK::NUP214 fusion
- Should not fulfill diagnostic criteria for a myeloid neoplasm postcytotoxic therapy
- DEK::NUP214 rearrangement can be detected by FISH or fusion transcripts by RT-PCR to support the diagnosis (Leukemia 2022;36:1703)
Laboratory
- Anemia
- Thrombocytopenia
- Pancytopenia
- Leukocytosis
- Reference: Leukemia 2022;36:1703
Prognostic factors
- This entity has poor prognosis and overall short survival (Leukemia 2022;36:1703)
- Presence of an FLT3 internal tandem duplication (ITD) is associated with faster relapse, although it has not shown to affect overall survival (Leukemia 2022;36:1703)
- Allogeneic stem cell transplantation improves the survival (Leukemia 2022;36:1703)
- According to the Children's Oncology Group, children with AML with DEK::NUP214 possess a poor outcome regardless of FLT3-ITD status (Br J Haematol 2014;166:254)
- Initial diagnosis of MDS versus AML and allogeneic hematopoietic stem cell transplantation have been shown to be prognostic factors for survival in patients with AML with DEK::NUP214 (Mod Pathol 2021;34:1143)
Case reports
- 15 year old boy diagnosed with AML with t(6;9)(p23;q34), DEK::NUP214 fusion underwent allogeneic transplant and showed full donor chimerism but developed AML with t(8;21) RUNX1::RUNX1T1 (EJHaem 2021;2:285)
- 16 year old boy diagnosed with AML with t(6;9)(p23;q34) developed a TBL1XR1::PDGFRB fusion following transplant, treated with dasatinib (Leuk Lymphoma 2017;58:2969)
- 23 year old woman who presented with fever and fatigue was found to have FIP1L1::PDGFRA and DEK::NUP214 fusion genes, treated with imatinib (Oncol Lett 2020;19:3587)
- 46 year old woman diagnosed with AML was found to have a t(1;9)(p22;q34), in which transcriptomic analysis identified a DEK::NUP214 fusion (Oncol Lett 2017;14:7021)
Treatment
- Allogeneic stem cell transplantation seems to improve survival (Leukemia 2022;36:1703, Blood 2019;134:5103)
Microscopic (histologic) description
- Bone marrow core biopsy is often hypercellular with a diffuse infiltration of immature mononuclear cells
- While basophilia has been a classic finding with this entity, it is not actually observed as frequently and tends to be mild (Mod Pathol 2021;34:1143, Int J Lab Hematol 2017;39:409)
- Dysplasia as present in almost all cases (Int J Lab Hematol 2017;39:409)
Microscopic (histologic) images
Contributed by Giby V. George, M.B.B.S.
Hypercellular bone marrow with diffuse immature mononuclear infiltrate
Skin with dermal periadnexal and perivascular mononuclear infiltrate
Skin with dermal periadnexal and perivascular mononuclear infiltrate
Peripheral smear description
- Blasts show features of maturation and sometimes myelomonocytic differentiation (Leukemia 2022;36:1703)
- Features of multilineage dysplasia is seen, including erythroid and myeloid progenitors, presence of ring sideroblasts and micromegakaryocytes (Leukemia 2022;36:1703)
- While basophilia has been a classic finding with this entity, it is not actually observed as frequently and tends to be mild (Mod Pathol 2021;34:1143, Int J Lab Hematol 2017;39:409)
Peripheral smear images
Contributed by Giby V. George, M.B.B.S.
Blasts with high N:C ratio
Blasts with high N:C ratio
Blasts with high N:C ratio
Intermediate to large blasts
Intermediate to large blasts
Flow cytometry description
- Blasts possess a nonspecific myeloid immunophenotype CD13, CD33, CD34, CD38, KIT (CD117), CD123, HLA-DR and myeloperoxidase (MPO) (Leukemia 2022;36:1703, Mod Pathol 2021;34:1143, Int J Lab Hematol 2017;39:409, Am J Clin Pathol 1997;107:430)
- CD7, CD15, CD64 and TdT are variably expressed and CD34 is usually negative (Leukemia 2022;36:1703)
Flow cytometry images
Contributed by Giby V. George, M.B.B.S.
Expanded CD45 dim, low side scatter gate
Molecular / cytogenetics description
- This subtype of AML is detection of t(6;9)(p22.3;q34.1) on karyotype or molecular confirmation of an in frame fusion of DEK on chromosome 6p22.3 and NUP214 (CAN) on 9q34.1, in which the oncogenic fusion occurs on derivative chromosome 6 (Leukemia 2022;36:1703)
- Detection of the DEK:NUP214 fusion product by RT-PCR can be used for molecular disease monitoring (Blood 2022;140:1345)
- Most often t(6;9)(p23;q34) is often the sole cytogenetic abnormality; trisomy 8 and a ring chromosome 12 have been reported (Am J Clin Pathol 1997;107:430)
- This translocation is often the sole alteration, although less commonly, a complex karyotype may be observed (Leukemia 2022;36:1703)
- Concurrent FLT3 ITD mutations occur in 50 - 88% of patients and RAS pathway gene mutations may be seen (Leukemia 2022;36:1703, N Engl J Med 2016;374:2209)
Molecular / cytogenetics images
Contributed by Giby V. George, M.B.B.S.
Karyotype
Videos
Understanding acute myeloid leukemia with DEK::NUP214 fusion: a comprehensive guide
Sample pathology report
- Peripheral blood, bone marrow aspirate, touch imprint, core biopsy and clot section:
- Acute myeloid leukemia with DEK::NUP214 fusion
- Peripheral blood: The blood smear shows pancytopenia with anisopoikilocytosis, including ovalocytes and few teardrop forms, as well as granulocytic dysplasia (hypogranular forms). Scattered blasts are visualized, which are intermediate to large with moderate basophilic cytoplasm, some with azurophilic granules. Nuclei are large and irregular, containing dispersed chromatin and few conspicuous nucleoli.
- Bone marrow aspirate and touch imprint: The bone marrow aspirate and touch imprint show abundant blasts with similar morphologic features as described above. Multilineage dysplasia is appreciated with irregular erythroid lobulation, micromegakaryocytes, hypogranularity and hypercondensation seen in myeloid progenitors.
- Bone marrow core biopsy: The bone marrow core biopsy is hypercellular for age (80 - 90%). There is extensive replacement of the marrow by sheets of immature mononuclear cells. Background hematopoiesis is markedly decreased with few scattered micromegakaryocytes.
- Clot section: The bone marrow clot section shows clotted erythrocytes with scattered immature mononuclear cells and few marrow elements.
Differential diagnosis
- Acute myeloid leukemia with other defining genetic abnormalities:
- Lacks DEK::NUP214 fusion
- Presence of other defining genetic features
- Acute myeloid leukemia, myelodysplasia related (AML MR):
- AML with DEK::NUP214 fusion is a genetically defined subtype of AML and this finding would supersede a diagnosis of AML MR
Board review style question #1
A 25 year old woman presents with worsening fatigue. Laboratory results are notable for pancytopenia and leukocytosis. A peripheral smear is obtained and submitted for pathology and flow cytometry evaluation. Peripheral smear showed scattered blasts and hypogranular neutrophils. Flow cytometry (not shown) reveals an expanded CD45 dim, low side scatter gate containing 12% of events with coexpression of CD34, CD38 (heterogeneous), CD200, CD7 (subset), CD13, HLA-DR (heterogeneous), CD123, CD117, CD33 and MPO (dim). Cytogenetic and molecular workup reveals a DEK::NUP214 fusion. Which of the following other peripheral smear findings is likely to be observed in this case?
- Basophilia
- Eosinophilia
- Monocytosis
- Target cells
Board review style answer #1
A. Basophilia is frequently observed in cases of AML with DEK::NUP214 fusion.
Answer B is incorrect because eosinophilia is more often seen in myeloproliferative neoplasms or other
myeloid neoplasms with specific genetic aberrations.
Answer D is incorrect because target cells are not typical of this entity.
Answer C is incorrect because monocytosis is not usually observed in this entity but may be observed in
myeloproliferative neoplasms or myelodysplastic / myeloproliferative neoplasms.
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Reference: AML with t(6;9)(p23;q34); DEK::NUP214
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Reference: AML with t(6;9)(p23;q34); DEK::NUP214
