The ITIM-containing receptor LAIR1 is essential for acute myeloid leukaemia development

Xunlei Kang; Zhigang Lu; Changhao Cui; Mi Deng Ph.D.; Yuqi Fan; Baijun Dong; Xin Han; Fuchun Xie; Jeffrey W. Tyner; John E. Coligan; Robert H Collins; Xiangshu Xiao; M. James You; Chengcheng Zhang

doi:10.1038/ncb3158

The ITIM-containing receptor LAIR1 is essential for acute myeloid leukaemia development

Xunlei Kang, Zhigang Lu, Changhao Cui, Mi Deng Ph.D., Yuqi Fan, Baijun Dong, Xin Han, Fuchun Xie, Jeffrey W. Tyner, John E. Coligan, Robert H Collins, Xiangshu Xiao, M. James You, Chengcheng Zhang

Research output: Contribution to journal › Article

55 Scopus citations

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	https://doi.org/10.1038/ncb3158
State	Published - May 5 2015

Fingerprint

ASJC Scopus subject areas

Cell Biology

Cite this

Kang, X., Lu, Z., Cui, C., Deng Ph.D., M., Fan, Y., Dong, B., Han, X., Xie, F., Tyner, J. W., Coligan, J. E., Collins, R. H., Xiao, X., You, M. J., & Zhang, C. (2015). The ITIM-containing receptor LAIR1 is essential for acute myeloid leukaemia development. Nature Cell Biology, 17(5), 665-677. https://doi.org/10.1038/ncb3158

The ITIM-containing receptor LAIR1 is essential for acute myeloid leukaemia development. / Kang, Xunlei; Lu, Zhigang; Cui, Changhao; Deng Ph.D., Mi; Fan, Yuqi; Dong, Baijun; Han, Xin; Xie, Fuchun; Tyner, Jeffrey W.; Coligan, John E.; Collins, Robert H; Xiao, Xiangshu; You, M. James; Zhang, Chengcheng.

In: Nature Cell Biology, Vol. 17, No. 5, 05.05.2015, p. 665-677.

Research output: Contribution to journal › Article

Kang, Xunlei ; Lu, Zhigang ; Cui, Changhao ; Deng Ph.D., Mi ; Fan, Yuqi ; Dong, Baijun ; Han, Xin ; Xie, Fuchun ; Tyner, Jeffrey W. ; Coligan, John E. ; Collins, Robert H ; Xiao, Xiangshu ; You, M. James ; Zhang, Chengcheng. / The ITIM-containing receptor LAIR1 is essential for acute myeloid leukaemia development. In: Nature Cell Biology. 2015 ; Vol. 17, No. 5. pp. 665-677.

@article{e5bdca46ff0c4ec78af4d7e092788c95,

title = "The ITIM-containing receptor LAIR1 is essential for acute myeloid leukaemia development",

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.",

author = "Xunlei Kang and Zhigang Lu and Changhao Cui and {Deng Ph.D.}, Mi and Yuqi Fan and Baijun Dong and Xin Han and Fuchun Xie and Tyner, {Jeffrey W.} and Coligan, {John E.} and Collins, {Robert H} and Xiangshu Xiao and You, {M. James} and Chengcheng Zhang",

year = "2015",

month = may,

day = "5",

doi = "10.1038/ncb3158",

language = "English (US)",

volume = "17",

pages = "665--677",

journal = "Nature Cell Biology",

issn = "1465-7392",

publisher = "Nature Publishing Group",

number = "5",

}

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 Ph.D., Mi

AU - Fan, Yuqi

AU - Dong, Baijun

AU - Han, Xin

AU - Xie, Fuchun

AU - Tyner, Jeffrey W.

AU - Coligan, John E.

AU - Collins, Robert H

AU - Xiao, Xiangshu

AU - You, M. James

AU - Zhang, Chengcheng

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.

UR - http://www.scopus.com/inward/record.url?scp=84928938594&partnerID=8YFLogxK

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 -

Access to Document

10.1038/ncb3158