1. ¹State Key Lab for Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
2. ²Leukemia Research Unit, JiangSu Institute of Hematology, First Hospital affiliated to Soochow University, Suzhou, P.R. China

Correspondence: Professor S-J Chen, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197, Ruijin Road II, Shanghai 200025, P.R. China. E-mail: sjchen@stn.sh.cn; Y-Q Xue, Leukemia Research Unit, JiangSu Institute of Hematology, First Hospital affiliated to Soochow University, 188 ShiZi Street, Suzhou 215006, P.R. China. E-mail: uujihsmc@public1.sz.js.cn

³These authors contributed equally to this work.

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

Received 14 August 2007; Revised 30 October 2007; Accepted 26 November 2007; Published online 17 December 2007.

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.