We therefore combined the FLT3/ITD mutation with a model of myelodysplastic syndrome involving transgenic expression of the Nup98-HoxD13 (NHD13) fusion gene.
NUP98 is known to be fused to at least 28 different partner genes in patients with hematopoietic malignancies, including acute myeloid leukemia, chronic myeloid leukemia in blast crisis, myelodysplastic syndrome, acute lymphoblastic leukemia, and bilineage/biphenotypic leukemia.
NUP98-HOXD13 (NHD13) fusions have been identified in patients with myelodysplastic syndrome, acute myelogenous leukemia and chronic myeloid leukemia blast crisis.
NUP98-HOXA9 is associated with the t(7;11)(p15;p15) translocation in acute myeloid leukemia (AML), myelodysplastic syndrome, and blastic crisis of chronic myeloid leukemia.
A novel gene, ANKRD28 on 3p25, is fused with NUP98 on 11p15 in a cryptic 3-way translocation of t(3;5;11)(p25;q35;p15) in an adult patient with myelodysplastic syndrome/acute myelogenous leukemia.
The t(7;11)(p15;p15) translocation, observed in acute myelogenous leukemia and myelodysplastic syndrome, generates a chimeric gene where the 5' portion of the sequence encoding the human nucleoporin NUP98 protein is fused to the 3' region of HOXA9.
Leukemic cells from the patient were found to express the fusion transcript of NUP98 and DDX10, which is in accordance with previously reported cases of de novo or therapy-related acute myelogenous leukemia and myelodysplastic syndrome with inv(11)(p15q22).
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.
This case is the third report of t(2;11) leukaemia with NUP98-HOXD13 and the first report showing that NUP98 rearrangements are associated with infant leukaemia, as well as therapy-related acute myelogenous leukaemia or myelodysplastic syndrome.