Acute Myeloid Leukemia (AML) with NUP214-ABL1

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Primary Author(s)*

Jessica Snider, M.D. and Daynna J. Wolff, Ph.D.

Cancer Category/Type

Acute Myeloid Leukemia

Cancer Sub-Classification / Subtype

NUP214/ABL1-Mediated Acute Myelomonocytic Leukemia

Definition / Description of Disease

A hematologic neoplasm comprised of myeloblasts that arise from the bone marrow due to amplification at 9q that has breakpoints in the ABL1 and NUP214 gene, resulting in a NUP214-ABL1 gene fusion. NUP214 is required for cell cycle and nucleocytoplasmic transport. The NUP214-ABL1 protein cannot activate the ABL1 tyrosine kinase unless it interacts and competes with other nuclear pore proteins and thus, the amplification of NUP214-ABL1 is necessary for neoplastic transformation and results in a constitutively activated tyrosine kinase with oncogenic potential[1][2]. This gene fusion has recently been identified in one case of acute myeloid leukemia (AML), and prognosis has yet to be determined in this single case.

Synonyms / Terminology

Acute myelocytic leukemia, acute myelogenous leukemia, acute granulocytic leukemia, acute non-lymphocytic leukemia

Epidemiology / Prevalence

One case of NUP214/ABL1-Mediated Acute Myelomonocytic Leukemia has been identified in a 64 year old male after initial treatment with FLT3-directed therapy. This translocation has also been observed in ~6% of all T-cell Acute Lymphoblastic Leukemias and only a few cases of B-cell Acute Lymphoblastic Leukemias[1].

Clinical Features

Fatigue, insomnia, dizziness, splenomegaly

Sites of Involvement

Peripheral blood and bone marrow

Morphologic Features

Leukocytosis consisting of blast-like cells with a high nuclear to cytoplasm ratio and open chromatin as well as mature monocytes can be observed in the peripheral smear. In the bone marrow, the myeloid series consists mostly of blast-like cells with minimal evidence of terminal differentiation. Rare erythroid elements and megakaryocytes may be seen.


Myeloblasts express dim CD45, dim CD34, dim CD117, HLA-DR, dim CD33, and dim CD13.

Finding Marker
Positive (universal) EXAMPLE CD1
Positive (subset) EXAMPLE CD2
Negative (universal) EXAMPLE CD3
Negative (subset) EXAMPLE CD4

Chromosomal Rearrangements (Gene Fusions)

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Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Pathogenic Derivative Prevalence
3'ABL1 / 5'NUP214 Rare

Characteristic Chromosomal Aberrations / Patterns

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Genomic Gain/Loss/LOH

Put your text here and/or fill in the table

Chromosome Number Gain/Loss/Amp/LOH Region
9q Amp Chr9:133728488-134083915

Additional findings in our case (may or may not be related to NUP214-ABL1 gene fusion):

Chromosome Number Gain/Loss/Amp/LOH Region
11q LOH Chr11:66206967-135006516
11q Amp LOH Chr11:118335673-118357315
21q Loss Chr21:36209650-36315003

Gene Mutations (SNV/INDEL)

In addition to the NUP214-ABL1 gene fusion, the single case identified showed focal deletion of exons 3-8 of RUNX1, loss of heterozygosity of 11q with nested gain of exons 2-10 of the KMT2A (MLL) gene. It is unknown whether or not these additional findings are related to the NUP214-ABL1 gene fusion.

Gene Mutation Oncogene/Tumor Suppressor/Other Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) Prevalence (COSMIC/TCGA/Other)

Other Mutations

Type Gene/Region/Other
Concomitant Mutations EXAMPLE IDH1 R123H
Secondary Mutations EXAMPLE Trisomy 7
Mutually Exclusive EXAMPLE EGFR Amplification

Epigenomics (Methylation)

Not applicable.

Genes and Main Pathways Involved

NUP214 (nucleoporin 214) is required for cell cycle and nucleocytoplasmic transport. The protein is located on the cytoplasmic side of the nuclear pore complex. The gene is located at band 9q34.1 and includes 36 exons (1-36). The NUP214-ABL1 protein cannot activate the ABL1 kinase unless it interacts and competes with other nuclear pore proteins and thus, the amplification of NUP214-ABL1 is necessary for neoplastic transformation, resulting in a constitutively activated tyrosine kinase with oncogenic potential[1][2].

RUNX1 is a transcription factor that regulates the differentiation of hematopoietic stem cells into mature blood cells. RUNX proteins form a heterodimeric complex with CBFβ which confers increased DNA binding and stability to the complex.

KMT2A encodes a transcriptional coactivator that plays an essential role in regulating gene expression during early development and hematopoiesis.

Diagnostic Testing Methods

Classical cytogenetics, FISH and molecular genetics.

Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)

No data has been reported on the prognosis of a NUP214-ABL1 fusion in AML. RUNX1 deletions have been reported to be an independent marker for a shorter event free survival, having a decreased overall survival and demonstrate resistance to chemotherapy[3]. The presence of a partial tandem duplication of the KMT2A gene has been reported to have an overall unfavorable prognosis with shorter remission with relapse generally occurring in the first year[4].

Familial Forms

No familial forms have been documented.

Other Information

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  1. 1.0 1.1 1.2 Zhou, Min-Hang; et al. (2014). "NUP214 fusion genes in acute leukemia (Review)". Oncology Letters. 8 (3): 959–962. doi:10.3892/ol.2014.2263. ISSN 1792-1074. PMC 4114590. PMID 25120641.
  2. 2.0 2.1 Duployez, Nicolas; et al. (2016). "NUP214-ABL1 fusion defines a rare subtype of B-cell precursor acute lymphoblastic leukemia that could benefit from tyrosine kinase inhibitors". Haematologica. 101 (4): e133–e134. doi:10.3324/haematol.2015.136499. ISSN 0390-6078. PMC 5004396. PMID 26681761.
  3. Takahashi, Shinichiro (2011). "Current findings for recurring mutations in acute myeloid leukemia". Journal of Hematology & Oncology. 4: 36. doi:10.1186/1756-8722-4-36. ISSN 1756-8722. PMC 3180439. PMID 21917154.
  4. Schnittger, S.; et al. (2000). "Screening for MLL tandem duplication in 387 unselected patients with AML identify a prognostically unfavorable subset of AML". Leukemia. 14 (5): 796–804. doi:10.1038/sj.leu.2401773. ISSN 0887-6924. PMID 10803509.


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