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t(1;11)(q24;p15) NUP98/PRRX1

Written2005-09Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers; CHU Poitiers Hospital, F-86021 Poitiers, France
Updated2018-01Adriana Zamecnikova
Kuwait Cancer Control Center, Kuwait

Abstract NUP98 is considered as one of the most promiscuous genes in hematologic malignancies due to its participation in chromosomal translocations with up to 30 different partner genes, including homeodomain transcription factors.

Keywords NUP98; acute myeloid leukemia; 11p15.5 translocations, therapy-related neoplasms.

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ICD-Topo C420,C421,C424
ICD-Morpho 9975/3 Chronic myelogenous leukaemia, BCR-ABL1 positive; Myeloproliferative neoplasm, unclassifiable; Myelodysplastic/myeloproliferative neoplasm, unclassifiable
ICD-Morpho 9945/3 Chronic myelomonocytic leukaemia
ICD-Morpho 9873/3 AML without maturation
ICD-Morpho 9874/3 AML with maturation
ICD-Morpho 9867/3 Acute myelomonocytic leukaemia
Atlas_Id 1169
Note Included are patients with 1q21-25 breakpoints and confirmed NUP98 rearrangement.
  Figure 1. Partial karyotypes with t(1;11)(q24;p15) (A). Fluorescence in situ hybridization with SureFISH NUP98 probe revealing rearrangement of the gene on metaphase and interphase cells (B)

Clinics and Pathology

Disease Acute myeloid leukemia (AML), probably treatment related and chronic myeloid leukemia (CML) in progression.
Etiology Acute myeloid leukemia in 4: 2 patients with AML with maturation (AML-M2), in 1 of them that developed 3 years after the start of chemotherapy (MACOP-B) for stage III non-Hodgkin lymphoma (NHL)(immunoblast type) (Nakamura et al., 1999; Hatano et al., 2000) and in the other it was diagnosed 3 years after chemotherapy (ifosfamide, adriamycin, cytoxan, etopside) and radiotherapy for sarcoma of the testis (Soares et al., 2006). 1 patient was diagnosed with AML with minimal maturation (AML-M1) who received chemotherapy (adriamycin, cytoxan, 5-FU) and bone marrow transplantation for breast adenocarcinoma (Kobzev et al., 2004), 1 with myelodysplastic syndrome evolving into acute myelomonocytic leukemia (M4) that developed after chemotherapy (doxorubicin, ifosfamide) and radiotherapy for liposarcoma with the latency period from chemotherapy to the onset of MDS (treated with azacytidine) 30 months and of AML 38 months (Zhang et al., 2007). 2 patients had CML in transformation, 1 of them on hydrea and myleran therapy (Kobzev et al., 2004) and the other received hydroxyurea during the chronic phase and chemotherapy (arabinosylcytosine, aclamycin, daunarubicin) during transformation that developed after 2.5 years of chronic phase (Bai et al., 2006). Our unpublished case received chemotherapy (MECOB-P) for B-cell NHL and developed chronic myelomonocytic leukemia (CMML) 18 month later.
Epidemiology 5 patients with confirmed NUP98 rearrangement (4 males and 1 female aged 42 to 74 years, median 51 years) (Hatano et al., 2000 Kobzev et al., 2004; Bai et al., 2006; Zhang et al., 2007) and an 18 years old male without molecular studies (Soares et al., 2006). NUP98 rearrangement was also detected in a 36 years old male (unpublished data).
Evolution In 1 AML-M2 patient, complete remission of leukemia was achieved, but the NHL relapsed and an advanced gastric carcinoma was found and the patient died shortly afterwards (Hatano et al., 2000) and the other patient with AML-M2 died 5 months after leukemia onset (Soares et al., 2006). The 2 other AML patients died shortly after the onset of leukemia (Kobzev et al., 2004; Zhang et al., 2007) as well as the patient with CML in transformation (Kobzev et al., 2004). From these data it appears that the clinical course of patients is quite aggressive and the prognosis is dismal.


Cytogenetics Morphological Patients had variable breakpoints assigned to chromosome 1q, but FISH and/or molecular studies confirmed the involvement of PRRX1 that is mapped to 1q24.2, therefore chromosome 1 breakpoints in patients were the same.
  Figure 2. Karyotype of our unpublished case with t(1;11)(q24;p15) (arrows).
Additional anomalies Sole anomaly in 1 AML (Kobzev et al., 2004) and in 1 patient during the MDS phase (Zhang et al., 2007); found in association with limited anomalies in the remaining AML patients: +8 (Zhang et al., 2007) and del(7q)/+8 subsequently acquired during MDS progression (Zhang et al., 2007). Sole additional anomaly to t(9;22)(q34;q11) in both progressed CML patients (Kobzev et al., 2004; Bai et al., 2006); found as the only karyotypic anomaly in our unpublished case.

Genes involved and Proteins

Note This translocation appears to be closely related to other translocations involving NUP98 and an homeodomain bearing protein, i.e. the t(2;11)(q31;p15),.with HOXD13 or with HOXD11 involvement, the t(7;11)(p15;p15),.with HOXA9 or with HOXA13 involvement, the t(9;11)(q34;p15), with PRRX2 involvement, and the t(11;12)(p15;q13) with HOXC11 or with HOXC13 involvement
Gene NamePRRX1 (paired related homeobox 1)
Location 1q24.2NOTE
Protein Part of a homeobox gene family that encode evolutionarily conserved transcription factors; contain the DNA binding homeodomain; function as a transcription factor and has a role in regulation of developmental processes. In contrast to clustered HOX genes, PRRX1 is not implicated in normal hematopoiesis or leukemogenesis; PRRX1 contains 5 exons spanning 76 kb; the homeodomain of PRRX1 is located in exon 2. Member of the paired family of homeobox proteins localized to the nucleus; functions as a transcription co-activator.
Gene NameNUP98 (Nucleoporin 98)
Location 11p15.4
Protein Encodes a 98 kDa nuclear pore transport protein that is a component of the nuclear pore complex mediating transport of mRNA and proteins between the nucleus and the cytoplasm. Two major NUP98 transcripts of 4.0 and 7.0 kb can be detected and several minor transcripts are produced through alternative splicing. Belongs to a subgroup of nuclear pore proteins characterized by phenylalanine-glycine repeats (FG repeats), located in the N-terminus which are docking sites for transport receptors that play role in transport through the nuclear pore complex; the C-terminal auto-proteolytic domain contain a GLEBS-like motif and a RNP binding motif, surrounded by charged residues; may also function as a nuclear localization signal (Bai et al., 2006).

Result of the chromosomal anomaly

Hybrid gene
Description 5'-NUP98/PRRX1-3'. In frame fusion of NUP98 exon 12 to PRRX1 exon 2; no reciprocal fusion transcript.
Fusion Protein
Description The juxtaposition of the part of the DNA-binding homeodomain of PRRX1 to the N-terminal GLFG repeats of NUP98 leads to the generation of leukemogenic NUP98/PRRX1 fusion protein; the PRRX1 homeodomain may be upregulated.
Oncogenesis Chromosomal translocations of the nucleoporin NUP98 gene have been described in de novo and therapy-related hematopoietic malignancies, in particular acute myeloid leukemia. The formation of chromosomal rearrangements that generate NUP98 fusion proteins suggests that aberrant expression of NUP98 fusion proteins may be a causal event for leukemic transformation. In all of the leukemia-associated NUP98 fusions described thus far, the FG repeats of NUP98 are always retained, thus they are capable of interacting with HDAC1 and CREBBP that may enable them to act as both trans-activators and trans-repressors. (Bai et al., 2006). NUP98/PRRX1 generated by t(1;11)(q24.2;p15.4) shares these features with other NUP98 chimeric proteins, suggesting that the FG repeats on its N-terminus possess a critical role in leukemic transformation. Notably, all described patients with this rearrangement had a history of malignant tumor and leukemia developed after chemotherapy with topoisomerase II inhibitors and alkylating agents. Therefore, it is likely that the NUP98 locus is vulnerable to genotoxic induced chromosomal rearrangements.

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.


Trans-repressive effect of NUP98-PMX1 on PMX1-regulated c-FOS gene through recruitment of histone deacetylase 1 by FG repeats
Bai XT, Gu BW, Yin T, Niu C, Xi XD, Zhang J, Chen Z, Chen SJ
Cancer Res 2006 May 1;66(9):4584-90
PMID 16651408
Translocation (1;11)(q23;p15), a novel simple variant of translocation (7;11)(p15;p15), in a patient with AML (M2) accompanied by non-Hodgkin lymphoma and gastric cancer
Hatano Y, Miura I, Kume M, Miura AB
Cancer Genet Cytogenet 2000 Feb;117(1):19-23
PMID 10700860
Analysis of translocations that involve the NUP98 gene in patients with 11p15 chromosomal rearrangements
Kobzev YN, Martinez-Climent J, Lee S, Chen J, Rowley JD
Genes Chromosomes Cancer 2004 Dec;41(4):339-52
PMID 15390187
NUP98 is fused to PMX1 homeobox gene in human acute myelogenous leukemia with chromosome translocation t(1;11)(q23;p15)
Nakamura T, Yamazaki Y, Hatano Y, Miura I
Blood 1999 Jul 15;94(2):741-7
PMID 10397741
Secondary acute myeloid leukemia with a t(1;11)(q23;p15) in an adolescent treated for testicular sarcoma
Soares EM, Santos N, de Araújo Silva Amaral B, Silva ML, Leite EP, Silva MO, Muniz MT, Ribeiro RC, de Morais VL, de Jesus Marques Salles T
Cancer Genet Cytogenet 2006 Aug;169(1):83-5
PMID 16875945
Rare t(1;11)(q23;p15) in therapy-related myelodysplastic syndrome evolving into acute myelomonocytic leukemia: a case report and review of the literature
Zhang L, Alsabeh R, Mecucci C, La Starza R, Gorello P, Lee S, Lill M, Schreck R
Cancer Genet Cytogenet 2007 Oct 1;178(1):42-8
PMID 17889707


This paper should be referenced as such :
Zamecnikova A
t(1;11)(q24;p15) NUP98/PRRX1;
Atlas Genet Cytogenet Oncol Haematol. in press
On line version :
History of this paper:
Huret, JL. t(1;11)(q23;p15). Atlas Genet Cytogenet Oncol Haematol. 2006;10(2):114-114.

Other genes implicated (Data extracted from papers in the Atlas) [ 1 ]

Genes NUP98

Translocations implicated (Data extracted from papers in the Atlas)

 t(1;11)(q23;p15) NUP98/PRRX1

External links

NUP98 (11p15.4) PRRX1 (1q24.2)

NUP98 (11p15.4) PRRX1 (1q24.2)

Mitelman databaset(1;11)(q23;p15) [Case List]    t(1;11)(q23;p15) [Transloc-MCList] NUP98/PRRX1 [Fusion-MCList]
arrayMap (UZH-SIB Zurich)Morph ( 9975/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9945/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9873/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9874/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9867/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
Mitelman databaseNUP98/PRRX1 [MCList]  NUP98 (11p15.4) PRRX1 (1q24.2)
TICdbNUP98/PRRX1  NUP98 (11p15.4) PRRX1 (1q24.2)
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