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.


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)

External Links