Abstract
Conventional strategies are not particularly successful in the treatment of leukaemia, and identification of signalling pathways crucial to the activity of leukaemia stem cells will provide targets for the development of new therapies. Here we report that certain receptors containing the immunoreceptor tyrosine-based inhibition motif (ITIM) are crucial for the development of acute myeloid leukaemia (AML). Inhibition of expression of the ITIM-containing receptor LAIR1 does not affect normal haematopoiesis but abolishes leukaemia development. LAIR1 induces activation of SHP-1, which acts as a phosphatase-independent signalling adaptor to recruit CAMK1 for activation of downstream CREB in AML cells. The LAIR1-SHP-1-CAMK1-CREB pathway sustains the survival and self-renewal of AML stem cells. Intervention in the signalling initiated by ITIM-containing receptors such as LAIR1 may result in successful treatment of AML.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 665-677 |
| Number of pages | 13 |
| Journal | Nature Cell Biology |
| Volume | 17 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 5 2015 |
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ASJC Scopus subject areas
- Cell Biology
Cite this
The ITIM-containing receptor LAIR1 is essential for acute myeloid leukaemia development. / Kang, Xunlei; Lu, Zhigang; Cui, Changhao; Deng, Mi; Fan, Yuqi; Dong, Baijun; Han, Xin; Xie, Fuchun; Tyner, Jeffrey; Coligan, John E.; Collins, Robert H.; Xiao, Xiangshu; You, M. James; Zhang, Cheng Cheng.
In: Nature Cell Biology, Vol. 17, No. 5, 05.05.2015, p. 665-677.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The ITIM-containing receptor LAIR1 is essential for acute myeloid leukaemia development
AU - Kang, Xunlei
AU - Lu, Zhigang
AU - Cui, Changhao
AU - Deng, Mi
AU - Fan, Yuqi
AU - Dong, Baijun
AU - Han, Xin
AU - Xie, Fuchun
AU - Tyner, Jeffrey
AU - Coligan, John E.
AU - Collins, Robert H.
AU - Xiao, Xiangshu
AU - You, M. James
AU - Zhang, Cheng Cheng
PY - 2015/5/5
Y1 - 2015/5/5
N2 - Conventional strategies are not particularly successful in the treatment of leukaemia, and identification of signalling pathways crucial to the activity of leukaemia stem cells will provide targets for the development of new therapies. Here we report that certain receptors containing the immunoreceptor tyrosine-based inhibition motif (ITIM) are crucial for the development of acute myeloid leukaemia (AML). Inhibition of expression of the ITIM-containing receptor LAIR1 does not affect normal haematopoiesis but abolishes leukaemia development. LAIR1 induces activation of SHP-1, which acts as a phosphatase-independent signalling adaptor to recruit CAMK1 for activation of downstream CREB in AML cells. The LAIR1-SHP-1-CAMK1-CREB pathway sustains the survival and self-renewal of AML stem cells. Intervention in the signalling initiated by ITIM-containing receptors such as LAIR1 may result in successful treatment of AML.
AB - Conventional strategies are not particularly successful in the treatment of leukaemia, and identification of signalling pathways crucial to the activity of leukaemia stem cells will provide targets for the development of new therapies. Here we report that certain receptors containing the immunoreceptor tyrosine-based inhibition motif (ITIM) are crucial for the development of acute myeloid leukaemia (AML). Inhibition of expression of the ITIM-containing receptor LAIR1 does not affect normal haematopoiesis but abolishes leukaemia development. LAIR1 induces activation of SHP-1, which acts as a phosphatase-independent signalling adaptor to recruit CAMK1 for activation of downstream CREB in AML cells. The LAIR1-SHP-1-CAMK1-CREB pathway sustains the survival and self-renewal of AML stem cells. Intervention in the signalling initiated by ITIM-containing receptors such as LAIR1 may result in successful treatment of AML.
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UR - http://www.scopus.com/inward/citedby.url?scp=84928938594&partnerID=8YFLogxK
U2 - 10.1038/ncb3158
DO - 10.1038/ncb3158
M3 - Article
C2 - 25915125
AN - SCOPUS:84928938594
VL - 17
SP - 665
EP - 677
JO - Nature Cell Biology
JF - Nature Cell Biology
SN - 1465-7392
IS - 5
ER -