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.
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.
Pan
Q
Q
State Key Lab for Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Zhu
Y-J
YJ
Gu
B-W
BW
Cai
X
X
Bai
X-T
XT
Yun
H-Y
HY
Zhu
J
J
Chen
B
B
Weng
L
L
Chen
Z
Z
Xue
Y-Q
YQ
Chen
S-J
SJ
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D015153:Blotting, Western; D019556:COS Cells; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002522:Chlorocebus aethiops; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008969:Molecular Sequence Data; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D010802:Phylogeny; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics; D020703:ras GTPase-Activating Proteins / Q000235:genetics*
C101203:IQ motif containing GTPase activating protein 1; D028861:Nuclear Pore Complex Proteins; C465451:Nup98 protein, human; D011993:Recombinant Fusion Proteins; D020703:ras GTPase-Activating Proteins