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
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
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在急性 T 淋巴细胞/髓性白血病中发现一个新的融合基因 NUP98-IQCG，具有 t(3;11)(q29q13;p15)del(3)(q29) 易位
作者：
NUP98参与了白血病的多次反复染色体重排。我们从一例携带t(3；11)(q29q13；p15)del(3)(Q29)的初治急性T淋巴细胞/髓系白血病中鉴定出一种新的含有G(IQCG)基因的NUP98和IQ基序之间的融合。IQCG有两个假定的螺旋线圈结构域和一个IQ结构域。融合蛋白中保留了NUP98的FG重复序列和IQCG的螺旋卷曲结构域。我们证明了NUP98-IQCG可以形成同源二聚体，与NUP98或IQCG异源二聚，结合共激活子和/或共抑制子，并在体外显示出转录活性。NUP98-IQCG的表达可抑制Ara-C诱导的32Dcl3细胞的凋亡，并部分阻断G-CSF诱导的粒细胞分化。克隆形成实验和连续重复实验表明，NUP98-IQCG能刺激细胞增殖，部分阻断造血干/祖细胞的分化，但不能单独诱导转化。综上所述，我们的数据表明，新发现的NUP98-IQCG融合蛋白可能在白血病的发生中发挥重要作用，但本身可能不足以诱发白血病。
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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影响因子：
5.3
作者：
L. Kasper;Paul K. Brindle;C. Schnabel;C. Pritchard;M. Cleary;J. V. van Deursen
通讯作者：
L. Kasper;Paul K. Brindle;C. Schnabel;C. Pritchard;M. Cleary;J. V. van Deursen
影响因子：
64.5
作者：
RADU, A;MOORE, MS;BLOBEL, G
通讯作者：
BLOBEL, G
影响因子：
3.5
作者：
S. Tosi;E. Ballabio;A. Teigler‐Schlegel;J. Boultwood;J. Bruch;J. Harbott
通讯作者：
S. Tosi;E. Ballabio;A. Teigler‐Schlegel;J. Boultwood;J. Bruch;J. Harbott
DOI：
10.32388/78qroa
发表时间：
2020-02
期刊：
Definitions
影响因子：
--
作者：
通讯作者：
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影响因子：
6.5
作者：
I. Panagopoulos;G. Kerndrup;N. Carlsen;B. Strömbeck;M. Isaksson;B. Johansson
通讯作者：
I. Panagopoulos;G. Kerndrup;N. Carlsen;B. Strömbeck;M. Isaksson;B. Johansson