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t(3;11)(p11;p15) NUP98::POU1F1

Written2017-11Yiming Zhong, Megan Piazza, and Shashi Shetty
Center for Human Genetics Laboratory, Department of Pathology, Case Western Reserve University/University Hospitals Cleveland Medical Center, Cleveland, OH.;;

Abstract Review on t(3;11)(p11;p15), with data on clinics, and the genes involved.

Keywords Chromosome 3; Chromosome 11; NUP98; POU1F1; Acute myeloid leukemia; Therapy-related leukemia.

(Note : for Links provided by Atlas : click)


ICD-Topo C420,C421,C424
ICD-Morpho 9867/3 Acute myelomonocytic leukaemia
ICD-Morpho 9920/3 Therapy-related myeloid neoplasms
Atlas_Id 1632

Clinics and Pathology

Disease Acute myeloid leukemia (AML)
Epidemiology Two cases to date. In the first case, a 57-year-old female was initially diagnosed with a breast adenocarcinoma and she developed therapy-related AML-M4 fourteen years later (Lisboa et al., 2013). In the second case, a 19-year-old white male was diagnosed with de novo AML-M4 (Walker et al., 2013).
Prognosis The first patient was treated with chemotherapy (cytarabine, daunorubicin, and cyclosporin) and a complete response was achieved. The patient showed evidence of relapse ten months later and died within five months after relapse (Lisboa et al., 2013). The second patient had complete remission (CR) after induction treatment with cytarabine and daunorubicin. The post-CR therapy included high-dose cytarabine, cytoxan, and etoposide. The patient had a disease-free survival of 92+ months and an overall survival of 92.9+ months (Walker et al., 2013).

Genes involved and Proteins

Gene NameNUP98 (nucleoporin 98)
Location 11p15
Protein A 98 kDa nucleoporin. It is a component of the nuclear pore complexes (NPCs) and participates in many cellular processes, including nuclear import, nuclear export, mitotic progression, and regulation of gene expression (Gough et al., 2011). NUP98 protein contains N-terminal Gly-Leu-Phe-Gly (GLGF) repeat domains and a C-terminal RNA binding domain. Translocations between this gene and many other partner genes have been observed in leukemias. Rearrangements typically result in fusion proteins with the N-terminal GLGF domain of this gene to the C-terminus of the partner gene and they seem to be associated with poor prognosis (Struski et al., 2017; Kearney, L 2002).
Gene NamePOU1F1 (POU class 1 homeobox 1)
Location 3p11
Protein POU1F1, also known as PIT1, is a member of the POU family of transcription factors. It regulates expression of several genes involved in pituitary development and hormone expression (Ingraham et al., 1998) and also plays a role in cell proliferation and differentiation (Costoya et al., 1998; Pellegrini et al., 2006). Deregulation of POU1F1 is implicated in pituitary adenoma, combined pituitary hormone deficiency, breast carcinoma, and acute myeloid leukemia (Franc et al., 2014; Gao et al., 2016). POU1F1 protein contains an N-terminal transactivation domain and a C-terminal DNA binding domain including a homeodomain (Franc et al., 2014).

Result of the chromosomal anomaly

Hybrid gene
  Figure A: Schematic representation of the genomic DNA breakpoint (arrow) of NUP98/POU1F1 and nucleotide sequence of the genomic breakpoint (Modified from Lisboa et el., 2013).
Description Description: 5' NUP98 - 3' POU1F1 was produced in the case reported by Lisboa et al. in 2013. The breakpoints were 7490 bp downstream of NUP98 exon 11 and 129 bp downstream of the start of POU1F1 exon 4 (Figure A). The POU1F1 exon 4 was not included in the mature NUP98/POU1F1 message RNA (Lisboa et al., 2013).
Fusion Protein
  Figure B: Schematic representation of the NUP98-POU1F1 fusion protein (Modified from Lisboa et el., 2013).
Description The NUP98/POU1F1 fusion protein contains the GLFG repeats of NUP98 and the homeodomian of POU1F1 (Figure B).
Oncogenesis It is expected that the expression of NUP98/POU1F1 fusion gene is under the control of NUP98 promoter, leading to POU1F1 overexpressioin which results in increased proliferation of leukemia cells. It is hypothesized that the FLT3-ITD mutation collaborates with NUP98/POU1F1 in malignant transformation (Lisboa et el., 2013).

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity:
you are welcome to submit a paper to our new Case Report section.


Correlation of Pit-1 gene expression and Pit-1 content with proliferation and differentiation in human myeloid leukemic cells
Costoya JA, García-Barros M, Gallego R, Señarís R, Arce VM, Devesa J
Exp Cell Res 1998 Nov 25;245(1):132-6
PMID 9828108
POU1F1 (POU class 1 homeobox 1)
Franc JL, Becquet D, Franè_ois-Bellan AM.
Atlas Genet Cytogenet Oncol Haematol. 2014;18(10):728-730.
Over-Expression of POU Class 1 Homeobox 1 Transcription Factor (Pit-1) Predicts Poor Prognosis for Breast Cancer Patients
Gao Z, Xue K, Zhang L, Wei M
Med Sci Monit 2016 Oct 31;22:4121-4125
PMID 27798557
NUP98 gene fusions and hematopoietic malignancies: common themes and new biologic insights
Gough SM, Slape CI, Aplan PD
Blood 2011 Dec 8;118(24):6247-57
PMID 21948299
A tissue-specific transcription factor containing a homeodomain specifies a pituitary phenotype
Ingraham HA, Chen RP, Mangalam HJ, Elsholtz HP, Flynn SE, Lin CR, Simmons DM, Swanson L, Rosenfeld MG
Cell 1988 Nov 4;55(3):519-29
PMID 2902928
POU1F1 (POU class 1 homeobox 1) NUP98 (nucleoporin 98 kDa)
Franc JL, Becquet D, François-Bellan AM. Kearney, L
Atlas Genet Cytogenet Oncol Haematol. 2014;18(10):728-730.
NUP98 (nucleoporin 98 kDa)
Kearney, L
Atlas Genet Cytogenet Oncol Haematol. 2002;6(3):193-196.
POU1F1 is a novel fusion partner of NUP98 in acute myeloid leukemia with t(3;11)(p11;p15)
Lisboa S, Cerveira N, Bizarro S, Correia C, Vieira J, Torres L, Mariz JM, Teixeira MR
Mol Cancer 2013 Jan 18;12:5
PMID 23332017
Involvement of the pituitary-specific transcription factor pit-1 in somatolactotrope cell growth and death: an approach using dominant-negative pit-1 mutants
Pellegrini I, Roche C, Quentien MH, Ferrand M, Gunz G, Thirion S, Bagnis C, Enjalbert A, Franc JL
Mol Endocrinol 2006 Dec;20(12):3212-27
PMID 16901973
NUP98 is rearranged in 3
Struski S, Lagarde S, Bories P, Puiseux C, Prade N, Cuccuini W, Pages MP, Bidet A, Gervais C, Lafage-Pochitaloff M, Roche-Lestienne C, Barin C, Penther D, Nadal N, Radford-Weiss I, Collonge-Rame MA, Gaillard B, Mugneret F, Lefebvre C, Bart-Delabesse E, Petit A, Leverger G, Broccardo C, Luquet I, Pasquet M, Delabesse E
8% of pediatric AML forming a clinical and molecular homogenous group with a poor prognosis Leukemia
PMID 27694926
New recurrent balanced translocations in acute myeloid leukemia and myelodysplastic syndromes: cancer and leukemia group B 8461
Walker A, Mrózek K, Kohlschmidt J, Rao KW, Pettenati MJ, Sterling LJ, Marcucci G, Carroll AJ, Bloomfield CD; Alliance for Clinical Trials in Oncology
Genes Chromosomes Cancer 2013 Apr;52(4):385-401
PMID 23225546


This paper should be referenced as such :
Yiming Zhong, Megan Piazza, Shashi Shetty
t(3;11)(p11;p15) NUP98/POU1F1
Atlas Genet Cytogenet Oncol Haematol. 2018;22(12):507-509.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Translocations implicated (Data extracted from papers in the Atlas)

 t(3;11)(p11;p15) NUP98/POU1F1

External links

Mitelman databaset(3;11)(p11;p15)
arrayMap (UZH-SIB Zurich)Morph ( 9867/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9920/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

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