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A new fusion gene NUP98-IQCG identified in an acute T-lymphoid/myeloid leukemia with a t(3;11)(q29q13;p15)del(3)(q29) translocation

Oncogene volume 27, pages 3414–3423 (2008)Cite this article

Abstract

NUP98 has been involved in multiple recurrent chromosome rearrangements in leukemia. We identified a novel fusion between NUP98 and IQ motif containing G (IQCG) gene from a de novo acute T-lymphoid/myeloid leukemia harboring t(3;11)(q29q13;p15)del(3)(q29). IQCG has two putative coiled-coil domains and one 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, heterodimerize with 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 and serial replating assays indicated that NUP98-IQCG was able to stimulate proliferation, partially block differentiation of hematopoietic stem/progenitor cells but was unable to confer transformation alone. Taken together, our data indicate that newly identified NUP98-IQCG fusion protein may play an essential role in leukemogenesis, but by itself may not be sufficient to induce leukemia.

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Acknowledgements

This work was supported in part by the Chinese National High Tech Program (863: 2006AA02A405), Chinese National Key Basic Research Project (973, 2004 CB 518606), National Natural Science Foundation of China (30471953, 30521003, 30571046), the Key Discipline program of Shanghai Municipal Education Commission (Y0201), Shanghai Municipal Commission for Science and Technology (06DZ22021) and Samuel Waxman Cancer Research Foundation Co-PI Program. We thank all members of SIH for their support, Dr Jian-Xiang Liu for his constructive discussion and Dr Arthur Zelent for his critical proofreading of this manuscript.

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Author notes

  1. Q Pan

    Present address: 4Current address: Department of Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, PR China.,

  2. Q Pan, Y-J Zhu, B-W Gu and X Cai: These authors contributed equally to this work.

Authors and Affiliations

  1. State Key Lab for Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China

    Q Pan, B-W Gu, X Cai, X-T Bai, H-Y Yun, J Zhu, B Chen, L Weng, Z Chen & S-J Chen

  2. Leukemia Research Unit, JiangSu Institute of Hematology, First Hospital affiliated to Soochow University, Suzhou, P.R. China

    Y-J Zhu & Y-Q Xue

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Correspondence to Y-Q Xue or S-J Chen.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Pan, Q., Zhu, YJ., Gu, BW. et al. A new fusion gene NUP98-IQCG identified in an acute T-lymphoid/myeloid leukemia with a t(3;11)(q29q13;p15)del(3)(q29) translocation. Oncogene 27, 3414–3423 (2008). https://doi.org/10.1038/sj.onc.1210999

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