Deletion of the RNA-editing enzyme ADAR1 causes regression of established chronic myelogenous leukemia in mice.
Deletion of the RNA-editing enzyme ADAR1 causes regression of established chronic myelogenous leukemia in mice.
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DOI：
10.1002/ijc.27851
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发表时间：
2013-04-15
影响因子：
6.4
通讯作者：
Wang, Qingde
中科院分区：
文献类型：
--
作者：
Steinman, Richard A.;Yang, Qiong;Gasparetto, Maura;Robinson, Lisa J.;Liu, Xiaoping;Lenzner, Diana E.;Hou, Jingzhou;Smith, Clayton;Wang, Qingde
Patients with chronic myelogenous leukemia (CML) respond well to tyrosine kinase inhibitors (TKIs) of the Bcr-Abl oncoprotein. However, intolerance and resistance to these agents remains a challenge, and TKI’s are unable to eradicate rare leukemia-initiating cells. Leukemia treatment would benefit from a better understanding of molecular signals that are necessary for the survival of leukemia-initiating cells but dispensable for normal hematopoietic stem cells. Leukemia-initiating cells in CML can arise from myeloid progenitor cells, a population that we have reported in normal hematopoiesis to depend on the RNA-editing enzyme ADAR1 (adenosine deaminase acting on RNA-1). We now report that Bcr-Abl transformed leukemic cells were ADAR1-dependent in a conditional ADAR1 knockout mouse model. ADAR1 deletion reversed leukocytosis and splenomegaly, and preferentially depleted primitive Lin-Sca+Kit+ (LSK) leukemic cells but not LSK cells lacking the leukemic oncoprotein. ADAR1 deletion ultimately normalized the peripheral white blood count, eliminating leukemic cells as assessed by PCR. These results uncover a novel requirement for ADAR1 in myeloid leukemic cells and indicate that ADAR1 may comprise a new molecular target for CML-directed therapeutics.
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影响因子：
3.5
作者：
Borchert GM;Gilmore BL;Spengler RM;Xing Y;Lanier W;Bhattacharya D;Davidson BL
通讯作者：
Davidson BL
识别广泛的超编辑人类RNA。
影响因子：
4.5
作者：
Carmi S;Borukhov I;Levanon EY
通讯作者：
Levanon EY
影响因子：
20.3
作者：
Konig, Heiko;Holyoake, Tessa L.;Bhatia, Ravi
通讯作者：
Bhatia, Ravi
影响因子：
5.7
作者：
Flanagan, James M.;Funes, Juan M.;Boshoff, Chris
通讯作者：
Boshoff, Chris
DOI：
10.1084/jem.189.9.1399
发表时间：
1999-05-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Li S;Ilaria RL Jr;Million RP;Daley GQ;Van Etten RA
通讯作者：
Van Etten RA