t(5;11)(q35;p15.5) NUP98/NSD1

2002-03-01   Lyndal Kearney 

1.Leukaemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK

Clinics and Pathology


de novo acute myeloid leukemia (AML)

Phenotype stem cell origin

No specific subtype. Only 5 cases reported to date (1 AML-M1, 2 AML-M2, 2 AML-M4)


all 5 reported cases were children or young adults (age range 3-18 years). Male: female ratio 1.5:1


Cytogenetics morphological

The t(5;11)(q35;p15.5) is not detectable by G-banding. Three cases were reported as cryptic t(5;11) associated with del(5q); a further two cases were identified in apparently normal karyotypes.

Cytogenetics molecular

In one FISH study using whole chromosome paints, three out of four cases of childhood AML with del(5q) as the sole cytogenetic abnormality were found to have a cryptic t(5;11). In a second study using chromosome-specific subtelomeric probes, two out of 31 children and young adults (19 years) with a normal G-banded karyotype were found to have a cryptic t(5;11).
Note: While the der(11) is detectable by single colour painting using chromosome 5 whole chromosome paint (WCP), the der(5) is not detectable using chromosome 11 WCP. Neither M-FISH or SKY can reliably detect the t(5;11).
Atlas Image
Fig 1. Identification of a cryptic t(5;11) using the M-TEL assay. Bone marrow metaphase from a normal karyotype AML child hybridized with the M-TEL1 probe set. Chromosomes 1, 3, 7, 9, 13, 15, 17, 19, 21 and X and Y probes were all correctly hybridized. However, one homologue of chromosome 5 has chromosome 11 material on the q arm (yellow), and the corresponding chromosome 11 homologue has chromosome 5 material on the p arm (green). This corresponds to a balanced translocation, t(5q;11p). The der(5) and der(11) are indicated by arrows.

Genes Involved and Proteins

Gene name
NUP98 (nucleoporin 98 kDa)
at least 8 different fusion partners for NUP98 in leukaemia
Dna rna description
Two major transcripts: 4.0 and 7.0 kb. The 4.0 kb transcript consists of 20 exons.
Protein description
98 kD protein. Component of the nuclear pore complex, which regulates nucleocytoplasmic transport of protein and RNA. Contains multiple phenylalanine-glycine (FG) repeats which act as docking sites for transport receptors.
Gene name
NSD1 (Nuclear receptor-binding, su (var), enhancer-of-zeste and trithorax domain-containing protein 1
Dna rna description
at least 21 exons, cDNA is 8552 bp, open reading frame of 8088 bp
Protein description
predicted protein of 2696 amino acids. Contains at least 6 functional domains: su(var)3-9, enhancer-of-zeste, trithorax (SET), proline-tryptophan-tryptophan-proline (PWWP-I, PWWP-II), plant homeodomain protein­finger domains (PHD-I, PHD-II, PHD-III) and ten putative nuclear localization signals.

Result of the Chromosomal Anomaly


reciprocal NSD1-NUP98 fusion also present in all cases tested


The NUP98 and NSD1 mRNA are fused in-frame joining nucleotides 1552 of NUP98 to nucleotide 3506 of NSD1. The reciprocal transcript fuses NSD1 and NUP98 mRNA in-frame joining nucleotide 3505 of NSD1 to nucleotide 1553 of NUP98.

Detection protocole

RT-PCR with sense NUP98-5 (5-TCTTGGTACAGGAGCCTTTG-3, and antisense NSD1-1 (5TCCAAAAGCCACTTGCTTGGC-3) primers
Atlas Image
Fig 2. Schematic representation of the NUP98-NSD1 fusion protein. The wild type NUP98 and NSD1 proteins are also shown. The putative NUP98-NSD1 fusion protein would retain the NH2 terminal region of NUP98 containing the phenylalanine-glycine (FG) repeat domains and the COOH terminal region of NSD1 containing the SET, SET domain associated cysteine-rich (SAC) and PHD finger domains.

Highly cited references

Pubmed IDYearTitleCitations
175894992007NUP98-NSD1 links H3K36 methylation to Hox-A gene activation and leukaemogenesis.171
218134472011NUP98/NSD1 characterizes a novel poor prognostic group in acute myeloid leukemia with a distinct HOX gene expression pattern.100
254649002014AF10 regulates progressive H3K79 methylation and HOX gene expression in diverse AML subtypes.80
278891852016NUP98 Fusion Proteins Interact with the NSL and MLL1 Complexes to Drive Leukemogenesis.59
235315172013NUP98/JARID1A is a novel recurrent abnormality in pediatric acute megakaryoblastic leukemia with a distinct HOX gene expression pattern.58
251453432014NUP98/NSD1 and FLT3/ITD coexpression is more prevalent in younger AML patients and leads to induction failure: a COG and SWOG report.28
236300192013NUP98-NSD1 gene fusion and its related gene expression signature are strongly associated with a poor prognosis in pediatric acute myeloid leukemia.23
323444272020CDK6 is an essential direct target of NUP98 fusion proteins in acute myeloid leukemia.21
305681732019Dasatinib and navitoclax act synergistically to target NUP98-NSD1+/FLT3-ITD+ acute myeloid leukemia.20
249514662014Potent co-operation between the NUP98-NSD1 fusion and the FLT3-ITD mutation in acute myeloid leukemia induction.19
314675322019Mutated WT1, FLT3-ITD, and NUP98-NSD1 Fusion in Various Combinations Define a Poor Prognostic Group in Pediatric Acute Myeloid Leukemia.17
129312272003Frequency of NUP98-NSD1 fusion transcript in childhood acute myeloid leukaemia.17
260714602015Acute Myeloid Leukemia With Myelodysplasia-Related Changes.15
229295222013Analysis of NUP98/NSD1 translocations in adult AML and MDS patients.15
328688952020Covalent inhibition of NSD1 histone methyltransferase.14
266843932016High PRDM16 expression identifies a prognostic subgroup of pediatric acute myeloid leukaemia correlated to FLT3-ITD, KMT2A-PTD, and NUP98-NSD1: the results of the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-05 trial.13
287108062017Clinical features and prognostic impact of PRDM16 expression in adult acute myeloid leukemia.12
268590782016Identification of MYC mutations in acute myeloid leukemias with NUP98-NSD1 translocations.12
249271332014A sensitive luminescent assay for the histone methyltransferase NSD1 and other SAM-dependent enzymes.12
239999212013NUP98-NSD1 fusion in association with FLT3-ITD mutation identifies a prognostically relevant subgroup of pediatric acute myeloid leukemia patients suitable for monitoring by real time quantitative PCR.12
293307462018Risk-stratified therapy for children with FLT3-ITD-positive acute myeloid leukemia: results from the JPLSG AML-05 study.8
179889902007A novel gene, ANKRD28 on 3p25, is fused with NUP98 on 11p15 in a cryptic 3-way translocation of t(3;5;11)(p25;q35;p15) in an adult patient with myelodysplastic syndrome/acute myelogenous leukemia.8
153822622004Cryptic insertion producing two NUP98/NSD1 chimeric transcripts in adult refractory anemia with an excess of blasts.8
329931152020Targeted Inhibition of the NUP98-NSD1 Fusion Oncogene in Acute Myeloid Leukemia.7
229457722013A rare but specific subset of adult AML patients can be defined by the cytogenetically cryptic NUP98-NSD1 fusion gene.6
118957892002A cryptic t(5;11)(q35;p15.5) in 2 children with acute myeloid leukemia with apparently normal karyotypes, identified by a multiplex fluorescence in situ hybridization telomere assay.6
345825592022The menin-MLL1 interaction is a molecular dependency in NUP98-rearranged AML.5
314734702019Rapid detection of chromosomal translocation and precise breakpoint characterization in acute myeloid leukemia by nanopore long-read sequencing.5
159512872005Screening for NUP98 rearrangements in hematopoietic malignancies by fluorescence in situ hybridization.5
307840602019Clinical and biological features of paediatric acute myeloid leukaemia (AML) with primary induction failure in the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-05 study.4
287764362018Chimeric NUP98-NSD1 transcripts from the cryptic t(5;11)(q35.2;p15.4) in adult de novo acute myeloid leukemia.3
253013312014Concealed dagger in FLT3/ITD+ AML.3
352176262022A PRC2-Kdm5b axis sustains tumorigenicity of acute myeloid leukemia.2
345750252021NSD1: A Lysine Methyltransferase between Developmental Disorders and Cancer.2
332849452020Acute erythroid leukemia is enriched in NUP98 fusions: a report from the Children's Oncology Group.2
346383012021Impact of KMT2A Rearrangement and CSPG4 Expression in Pediatric Acute Myeloid Leukemia.2
311345092019Successful treatment of acute myeloid leukemia co-expressing NUP98/NSD1 and FLT3/ITD with preemptive donor lymphocyte infusions.2
328158762021NUP98-NSD1 Driven MDS/MPN in Childhood Masquerading as JMML.1
350739462022SMARCA5 interacts with NUP98-NSD1 oncofusion protein and sustains hematopoietic cells transformation.1
337840312021Mixed phenotype acute leukemia in a child associated with a NUP98-NSD1 fusion and NRAS p.Gly61Arg mutation.1
323785742020[Gilteritinib for pediatric FLT3 internal tandem duplication-positive recurrent acute myeloid leukemia].1
315508092019[Genetic characteristics and clinical outcomes of pediatric acute myeloid leukemia with NUP98-NSD1 fusion gene].1
258602352016A unique acute myeloid leukemia patient with cryptic NUP98-NSD1 gene and ASXL1 mutation.1
180685322008NUP98-NSD1 fusion by insertion in acute myeloblastic leukemia.1
355665032022Genetic Characteristics According to Subgroup of Acute Myeloid Leukemia with Myelodysplasia-Related Changes.0
342454962021Pediatric acute myeloid leukemia co-expressing FLT3/ITD and NUP98/NSD1 treated with gilteritinib plus allogenic peripheral blood stem cell transplantation: A case report.0
335363672021The First Korean Case of NUP98-NSD1 and a Novel SNRK-ETV6 Fusion in a Pediatric Therapy-related Acute Myeloid Leukemia Patient Detected by Targeted RNA Sequencing.0
333174362020Hyperleukocytosis predicts inferior clinical outcome in pediatric acute myeloid leukemia.0
303783132018[Molecular Characteristics and Clinical Features of Adults with NUP98 Fusions in Acute Myeloid Leukemia].0


Pubmed IDLast YearTitleAuthors
109590882000Potential role for DNA topoisomerase II poisons in the generation of t(11;20)(p15;q11) translocations.Ahuja HG et al
118957892002A cryptic t(5;11)(q35;p15.5) in 2 children with acute myeloid leukemia with apparently normal karyotypes, identified by a multiplex fluorescence in situ hybridization telomere assay.Brown J et al
112836802001Subtelomeric chromosome rearrangements are detected using an innovative 12-color FISH assay (M-TEL).Brown J et al
96288761998Two distinct nuclear receptor interaction domains in NSD1, a novel SET protein that exhibits characteristics of both corepressors and coactivators.Huang N et al
114934822001A novel gene, NSD1, is fused to NUP98 in the t(5;11)(q35;p15.5) in de novo childhood acute myeloid leukemia.Jaju RJ et al
103977451999A new recurrent translocation, t(5;11)(q35;p15.5), associated with del(5q) in childhood acute myeloid leukemia. The UK Cancer Cytogenetics Group (UKCCG).Jaju RJ et al
108692332000An optimized set of human telomere clones for studying telomere integrity and architecture.Knight SJ et al
117331442001Molecular characterization of NSD1, a human homologue of the mouse Nsd1 gene.Kurotaki N et al
116814082001NUP98 gene fusions in hematologic malignancies.Lam DH et al


Fusion gene

NUP98/NSD1 NUP98 (11p15.4) NSD1 (5q35.2) M ins(5;11)(q35;p15p13) t(5;11)(q35;p15) t(5;11;12)(q35;p15;q24)|NUP98/NSD1 NUP98 (11p15.4) NSD1 (5q35.2) TF LAML|NUP98/NSD1 NUP98 (11p15.4) NSD1 (5q35.2) TIC


Lyndal Kearney

t(5;11)(q35;p15.5) NUP98/NSD1

Atlas Genet Cytogenet Oncol Haematol. 2002-03-01

Online version: http://atlasgeneticsoncology.org/haematological/1209/t(5;11)(q35;p15-5)