t(7;11)(p15;p15) NUP98/HOXA13

2016-12-01   Aurelia M. Meloni-Ehrig  

1.CSI Laboratories, Alpharetta, GA. [email protected]

Abstract

Several t(7;11)(p15;p15) have been reported in myeloid neoplasms. The most common is the one leading to a fusion between the NUP98 (11p15) and the HOXA9 (7p15). A more rare t(7;11) is the one that leads to a fusion between the NUP98 and the HOXA13 gene on 7p15. This particular t(7;11) is associated primarily with acute myeloid leukemia (AML), primarily FAB M2 and M4. However, it has been reported also in one case of chronic myelogenous leukemia (CML) in blast crisis. The NUP98/HOXA13 fusion protein is thought to promote leukemogenesis through inhibition of HOXA13-mediated terminal differentiation and/or aberrant nucleocytoplasmic transport. . The protein encoded by the NUP98/HOXA13 fusion gene is similar to the one encoded by the NUP98/HOXA9 fusion, and the expression pattern of the HOXA13 gene in leukemic cell lines is similar to that of the HOXA9 gene, suggesting that the NUP98/HOXA13 fusion protein may play a role in leukemogenesis through a mechanism similar to that of the NUP98/HOXA9 fusion protein.

Clinics and Pathology

Noted

This rare t(7;11) has been reported in:
Acute myeloid leukemia (AML)
Chronic myelogenous leukemia (CML) in blast crisis

Disease

Acute myeloid leukemia (AML)

Phenotype stem cell origin

The blasts expressed CD7, CD11b, CD13, CD33, CD34, and HLADR antigens.

Clinics

De novo AML reported in a single patient, a 57 year-old woman (Taketani et al, 2002). The patient presented with leukocytosis (118,800/ µL) and 81% myeloid blasts.

Cytogenetics

At diagnosis, the karyotype was 46,XX,t(7;11)(p15;p15) in all 20 metaphase cells examined from a bone marrow sample. At remission, all 20 metaphase cells obtained from the bone marrow were normal, 46,XX. The t(7;11) seems to be a solitary abnormality in AML. No additional abnormalities have been reported so far.

Treatment

Patient received induction therapy with idarubicin and cytarabine (AraC), followed by multiple cycles of AraC and anthracyclines.

Evolution

A relapse occurred in the central nervous system 6 months after diagnosis and in the bone marrow 8 months after diagnosis, and the patient died of progressive disease 16 months after onset.

Prognosis

The prognosis in this single case of AML is unfavorable.

Disease

Chronic myelogenous leukemia (CML) in blast crisis

Epidemiology

This is the only described case so far of a CML in blast crisis presenting with a t(7;11)(p15;p15) in addition to the t(9;22)(q34;q11.2) (Di Giacomo et al., 2014).

Clinics

The patient is a 39 year-old man referred for leukocytosis, mild anemia, thrombocytopenia, and splenomegaly. CML in blast crisis was diagnosed on peripheral blood and bone marrow smears.

Cytogenetics

Chromosome analysis showed the following karyotype: 46,XY,t(9;22)(q34;q11.2)[6]/46,idem,t(7;11)(p15;p15)[9].

Treatment

Patient was treated initially with hydroxyurea, followed by Dasatinib but did not respond. High-dose ARA-C and subsequent bone marrow transplantation from a HLA haploidentical brother, were also unsuccessful.

Prognosis

The prognosis in this single case of CML in blast crisis is unfavorable.

Genes Involved and Proteins

Gene name
HOXA13 (homeobox A13)
Location
7p15.2
Note
he HOXA13 gene is part of the HOXA cluster genes and contains 2 exons, encoding a protein of 338 amino acids with a homeodomain.
Gene name
NUP98 (nucleoporin 98 kDa)
Location
11p15.4
Protein description
920 amino acids; 97 kDa; contains repeated motifs (GLFG and FG) in N-term and a RNA binding motif in C-term.

Result of the Chromosomal Anomaly

Description

The NUP98/HOXA13 fusion protein consists of the N-terminal phenylalanine-glycine repeat motif of NUP98 and the C-terminal homeodomain of HOXA13, similar to the NUP98/HOXA9 fusion protein (Fujino et al., 2002; Romana et al, 2006).

Highly cited references

Pubmed IDYearTitleCitations
249711562014Blast crisis Ph+ chronic myeloid leukemia with NUP98/HOXA13 up-regulating MSI2.23
121125332002The chromosome translocation t(7;11)(p15;p15) in acute myeloid leukemia results in fusion of the NUP98 gene with a HOXA cluster gene, HOXA13, but not HOXA9.0
236300192013NUP98-NSD1 gene fusion and its related gene expression signature are strongly associated with a poor prognosis in pediatric acute myeloid leukemia.0

Article Bibliography

Pubmed IDLast YearTitleAuthors
249711562014Blast crisis Ph+ chronic myeloid leukemia with NUP98/HOXA13 up-regulating MSI2.Di Giacomo D et al
118304962002Single-translocation and double-chimeric transcripts: detection of NUP98-HOXA9 in myeloid leukemias with HOXA11 or HOXA13 breaks of the chromosomal translocation t(7;11)(p15;p15).Fujino T et al
24041301990Quantification of neonatal cerebral ventricular volume by real-time ultrasonography. Derivation and in vitro confirmation of a mathematical model.Brann BS 4th et al
121125332002The chromosome translocation t(7;11)(p15;p15) in acute myeloid leukemia results in fusion of the NUP98 gene with a HOXA cluster gene, HOXA13, but not HOXA9.Taketani T et al

Summary

Fusion gene

NUP98/HOXA13

Note

Precise breakpoints are the following: t(7;11)(p15.2;p15.4).
Atlas Image
46,XX,t(7;11)(p15;p15)

Citation

Aurelia M. Meloni-Ehrig

t(7;11)(p15;p15) NUP98/HOXA13

Atlas Genet Cytogenet Oncol Haematol. 2016-12-01

Online version: http://atlasgeneticsoncology.org/haematological/1360/t(7