t(2;11)(q31;p15) NUP98/HOXD13
t(2;11)(q31;p15) NUP98/HOXD11

2013-03-01   Anwar N Mohamed 

1.Cytogenetics Laboratory, Pathology Department, Wayne State University School of Medicine, Detroit Medical Center, Detroit MI, USA

Clinics and Pathology


t(2;11)(q31;p15) is a rare but nonrandom translocation, reported in de novo acute myeloid leukemia (AML) as well as therapy related myelodysplastic syndrome/therapy related acute myeloid leukemia (t-MDS/t-AML), and one case of chronic myeloid leukemia in blast crisis (CML-BC).

Phenotype stem cell origin

Mostly AML-M4; bone marrow displaying monocytic features; AML-M6 in one case.


Generally the incidence of NUP98 rearrangements in leukemia is difficult to estimate probably 1-2% of AML cases. The t(2;15)(q32;p15) is rare; around 8 cases in literature; reported in male and female with 1:1 ratio; Infants under the age of a year; children (10-15 years) as well as adults (59-62 years); over-representation in Asian race in particular Japanese.
It has been shown that NUP98/11p15 is a frequent target for chromosomal rearrangements following chemotherapies with DNA topoisomerase II inhibitors. Interestingly, there are at least three infants leukemia with NUP98-HOXD13 gene fusion. It has been suggested that a high intake of certain diets rich in flavonoids during pregnancy increases the risk of infant leukemia due to the inhibition effect on topo II activity. It is worth to mention that in one infant, the NUP98-HOXD13 gene fusion was demonstrated retrospectively in neonatal blood spot. This provides strong evidence that the fusion is a prenatal event.


Peripheral blood; High white cell counts (WBC) with elevated monocytes; low platelets;
Bone Marrow: Hypercellular marrow with monocytic differentiation;
Immunophenotypes; Cell surface marker expression included CD13, CD14, CD33, CD34, HLA-DR, CD11b, CD65.


Due to rarity of t(2;11) leukemia, it is difficult to determine the prognostic significance of this translocation in leukemia. However, all de novo t(2;11) AML achieved remission, while patients with t-AML progressed rapidly. Generally, NUP98 gene fusion in leukemia predicts poor clinical outcome.


Cytogenetics morphological

Sole Anomaly; t(2;11)(q31;p15) was a sole anomaly in 5/8 cases.

Additional anomalies

Trisomy 8 in one case; balanced translocations in one case; in a CML-BC case t(2;11)(q31;p15) was secondary to Ph chromosome.


t(2;11;9)(q31;p15;q22)/NUP98-HOXD13 fusion in one case.

Genes Involved and Proteins

Gene name
HOXD13 (homeobox D13)
Dna rna description
HOXD11 and HOXD13 genes, located on chromosome 2q31, are member of a large family of developmental homeobox genes. Homeobox genes encode evolutionarily conserved transcription factors that appear to be involved in body plan formation and embryonic development, and also play a critical role in limb development. , In leukemia, there are at least 29 different partner genes fused with NUP98, 50% of which are homeobox genes. Different genes are likely associated with different leukemic phenotypes.
Gene name
HOXD11 (homeobox D11)
Dna rna description
See above.
Gene name
NUP98 (nucleoporin 98 kDa)
Dna rna description
NUP98 gene, located on chromosome 11p15, encodes a 98-KD protein a component of nuclear pore complex (NPC). NUP98 is found in the nucleoplasmic and cytoplasmic domains of the NPC, and functions as a transport co-factor of RNA and protein between the nucleus and cytoplasm. In addition, NUP98 appear to be involved in mitotic spindle formation and in cell cycle progression. Haploinsufficiency of NUP98 gene has been shown to cause premature separation of sister chromatids leading to sever aneuploidy.

Result of the Chromosomal Anomaly


5-NUP98-HOXD13-3 fusion is the oncogeneic product of the t(2;11); exon 12 of NUP98 gene is fused in-frame with exon 2 of HOXD13 gene.NUP98 fusion gene encodes a chimeric protein which is the amino terminal portion of NUP98 protein fuses the carboxyl portion of the partner gene HOXD13. The fused protein acts as an aberrant transcription factor. Several studies have demonstrated that NUP98-HOXD13 fusion protein blocks differentiation of hematopoietic precursor cells, and has aberrant self-renewal capacity.


Pubmed IDLast YearTitleAuthors
109950092000Heterogenous fusion transcripts involving the NUP98 gene and HOXD13 gene activation in a case of acute myeloid leukemia with the t(2;11)(q31;p15) translocation.Arai Y et al
214942612011Backtracking to birth of the NUP98-HOXD13 gene fusion in an infant acute myeloid leukemia.Emerenciano M et al
219482992011NUP98 gene fusions and hematopoietic malignancies: common themes and new biologic insights.Gough SM et al
176562572007A complex karyotype, including a three-way translocation generating a NUP98-HOXD13 transcript, in an infant with acute myeloid leukemia.Hidaka E et al
153901872004Analysis of translocations that involve the NUP98 gene in patients with 11p15 chromosomal rearrangements.Kobzev YN et al
97666501998NUP98-HOXD13 gene fusion in therapy-related acute myelogenous leukemia.Raza-Egilmez SZ et al
117823542002The HOXD11 gene is fused to the NUP98 gene in acute myeloid leukemia with t(2;11)(q31;p15).Taketani T et al


Fusion gene

NUP98/HOXD13 NUP98 (11p15.4) HOXD13 (2q31.1) M t(2;11)(q31;p15)|NUP98/HOXD13 NUP98 (11p15.4) HOXD13 (2q31.1) TIC , NUP98/HOXD13 NUP98 (11p15.4) HOXD13 (2q31.1) M t(2;11)(q31;p15)|NUP98/HOXD13 NUP98 (11p15.4) HOXD13 (2q31.1) TIC


t(2;11)(q31;p15) is an example of a variant translocation involving NUP98 gene at 11p15 which is fused with HOXD13 gene at 2q31. This fusion produces a chimeric protein with leukemogenic activity. t(2;11)(q31;p15) is associated with myeloid malignancies.
Atlas Image
Partial ideogram and G-banded karyotypes showing t(2;11)(q31;p15); arrows indicate breakpoints.


Anwar N Mohamed

t(2;11)(q31;p15) NUP98/HOXD13
t(2;11)(q31;p15) NUP98/HOXD11

Atlas Genet Cytogenet Oncol Haematol. 2013-03-01

Online version: http://atlasgeneticsoncology.org/haematological/1353/t(2;11)(q31;p15)

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