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

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

Research output: Contribution to journalArticle

45 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)665-677
Number of pages13
JournalNature Cell Biology
Volume17
Issue number5
DOIs
StatePublished - May 5 2015

Fingerprint

Immunoreceptor Tyrosine-Based Inhibition Motif
Acute Myeloid Leukemia
Leukemia
Myeloid Progenitor Cells
Hematopoiesis
Myeloid Cells
Phosphoric Monoester Hydrolases
Stem Cells
leukocyte-associated immunoglobulin-like receptor 1

ASJC Scopus subject areas

  • Cell Biology

Cite this

Kang, X., Lu, Z., Cui, C., Deng, M., Fan, Y., Dong, B., ... Zhang, C. 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, 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 journalArticle

Kang, X, Lu, Z, Cui, C, Deng, M, Fan, Y, Dong, B, Han, X, Xie, F, Tyner, J, Coligan, JE, Collins, RH, Xiao, X, You, MJ & Zhang, CC 2015, 'The ITIM-containing receptor LAIR1 is essential for acute myeloid leukaemia development', Nature Cell Biology, vol. 17, no. 5, pp. 665-677. https://doi.org/10.1038/ncb3158
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. / 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{9b3fe85f294f40099b242ade1e3fe2b6,
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 Mi Deng and Yuqi Fan and Baijun Dong and Xin Han and Fuchun Xie and Jeffrey Tyner and Coligan, {John E.} and Collins, {Robert H.} and Xiangshu Xiao and You, {M. James} and Zhang, {Cheng Cheng}",
year = "2015",
month = "5",
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, 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.

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

VL - 17

SP - 665

EP - 677

JO - Nature Cell Biology

JF - Nature Cell Biology

SN - 1465-7392

IS - 5

ER -