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 W. Tyner; John E. Coligan; Robert H. Collins; Xiangshu Xiao; M. James You; Cheng Cheng 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, Yuqi Fan, Baijun Dong, Xin Han, Fuchun Xie, Jeffrey W. Tyner, John E. Coligan, Robert H. Collins, Xiangshu Xiao, M. James You, Cheng Cheng Zhang

Research output: Contribution to journal › Article

63 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

ASJC Scopus subject areas

Cell Biology

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Kang, X., Lu, Z., Cui, C., Deng, 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. 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 W.; 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

Kang, Xunlei ; Lu, Zhigang ; Cui, Changhao ; Deng, Mi ; Fan, Yuqi ; Dong, Baijun ; Han, Xin ; Xie, Fuchun ; Tyner, Jeffrey W. ; 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.

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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.",

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