NUP98-HOXD13 gene fusion in therapy-related acute myelogenous leukemia.

Abstract

A novel chromosomal translocation, t(2;11)(q31;p15), was identified in a patient with therapy-related acute myelogenous leukemia (t-AML). Fluorescence in situ hybridization experiments mapped the breakpoint near NUP98; Southern blot analysis demonstrated that the nucleoporin gene NUP98 was disrupted by this translocation. We used rapid amplification of cDNA ends to identify a chimeric mRNA. An in-frame, chimeric mRNA that fused NUP98 sequences to the homeobox gene HOXD13 was cloned; the predicted fusion protein contains both the GLFG repeats from NUP98 as well as the homeodomain from HOXD13. The NUP98-HOXD13 fusion is structurally similar to the NUP98-HOXA9 fusion previously identified in patients with AML, leading to the speculation that NUP98-homeobox gene fusions may be oncogenic. Moreover, this report, along with a recent study that demonstrated NUP98-DDX10 fusions in patients with t-AML, raises the possibility that NUP98 may be a previously unsuspected target for chromosomal translocations in patients with t-AML.

• Authors: S Z Raza-Egilmez, S N Jani-Sait, M Grossi, M J Higgins, T B Shows, P D Aplan
• Journal: Cancer research (Cancer Res) Vol. 58 Issue 19 Pg. 4269-73 (Oct 01 1998) ISSN: 0008-5472 [Print] United States
• PMID: 9766650 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• HOXD13 protein, human
• Homeodomain Proteins
• Membrane Proteins
• Nuclear Pore Complex Proteins
• Nuclear Proteins
• Recombinant Fusion Proteins
• Transcription Factors
• nuclear pore complex protein 98

Topics

• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Artificial Gene Fusion
• Bone Marrow Cells (pathology)
• Child
• Chromosome Mapping
• Chromosomes, Human, Pair 11
• Chromosomes, Human, Pair 2
• Gene Rearrangement
• Homeodomain Proteins (biosynthesis, genetics)
• Humans
• In Situ Hybridization, Fluorescence
• Karyotyping
• Leukemia, Myeloid, Acute (chemically induced, genetics)
• Male
• Membrane Proteins (biosynthesis, genetics)
• Neoplasms, Second Primary (chemically induced, genetics)
• Nuclear Pore Complex Proteins
• Nuclear Proteins (biosynthesis, genetics)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy)
• Recombinant Fusion Proteins (biosynthesis)
• Transcription Factors
• Translocation, Genetic