NUP98 gene fusions in hematologic malignancies.
Acute leukemia is associated with a wide spectrum of recurrent, non-random chromosomal translocations. Molecular analysis of the genes involved in these translocations has led to a better understanding of both the causes of chromosomal rearrangements as well as the mechanisms of leukemic transformation. Recently, a number of laboratories have cloned translocations involving the NUP98 gene on chromosome 11p15.5, from patients with acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), chronic myelogenous leukemia (CML), and T cell acute lymphoblastic leukemia (T-ALL). To date, at least eight different chromosomal rearrangements involving NUP98 have been identified. The resultant chimeric transcripts encode fusion proteins that juxtapose the N-terminal GLFG repeats of NUP98 to the C-terminus of the partner gene. Of note, several of these translocations have been found in patients with therapy-related acute myelogenous leukemia (t-AML) or myelodysplastic syndrome (t-MDS), suggesting that genotoxic chemotherapeutic agents may play an important role in generating chromosomal rearrangements involving NUP98.
Lam
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Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, USA.
Aplan
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D019677:Artificial Gene Fusion; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D008954:Models, Biological; D009190:Myelodysplastic Syndromes / Q000235:genetics; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D014178:Translocation, Genetic
D018398:Homeodomain Proteins; D028861:Nuclear Pore Complex Proteins; D015514:Oncogene Proteins, Fusion; C093350:nuclear pore complex protein 98