NUP98 has been involved in multiple recurrent chromosome rearrangements in leukemia. We identified a novel fusion between NUP98 and IQ motif containing G (IQCG) from a de novo acute T/myeloid leukemia harboring t(3;11)(q29q13;p15). IQCG has 2 putative coiled-coil domains and an IQ domain. The FG repeat from NUP98 and the coiled-coil domain from IQCG were retained in the fusion protein. We demonstrated that NUP98-IQCG could form homodimer or heterodimerize with either NUP98 or IQCG, bind Co-activators and/or Co-repressors, and show transcriptional activity in vitro. Expression of NUP98-IQCG inhibited 32Dcl3 cell apoptosis induced by Ara-C, and partially blocked granulocyte differentiation induced by G-CSF. Colony forming assay also indicated that NUP98-IQCG was able to stimulate proliferation and partially block differentiation of hematopoietic stem/progenitor cells. We conclude that NUP98-IQCG may play an essential role in leukemogenesis by stimulating progenitor cell proliferation and inhibiting differentiation and apoptosis.

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