TY - JOUR
T1 - Leukocyte-associated Ig-like receptor-1 prevents granulocyte-monocyte colony stimulating factor-dependent proliferation and Akt1/PKB alpha activation in primary acute myeloid leukemia cells
AU - Zocchi, M. Raffaella
AU - Pellegatta, Fabio
AU - Pierri, Ivana
AU - Gobbi, Marco
AU - Poggi, Alessandro
PY - 2001
Y1 - 2001
N2 - The leukocyte-associated Ig-like receptor-1 (LAIR-1), a surface leukocyte receptor containing two immune receptor tyrosine-based inhibitory motif (ITIM) is expressed on acute myeloid leukemia (AML) blasts isolated from peripheral blood or bone marrow of 17 patients (2 MO, 3 M1, 5 M2, 2 M4 and 5 M5 acording to French, American and British classification). Further, we provide evidence that LAIR-1 engagement inhibits granulocyte-monocyte colony-stimulating factor (GM-CSF)-induced proliferation of AML blasts. Indeed, leukemia cells stimulated with GM-CSF were blocked in the G0/G1 phase of the cell cycle and underwent apoptosis within 4 days after the engagement of LAIR-1. Remarkably, LAIR-1 was functional also in AML blasts which do not express CD33, mainly M4 and M5. Importantly, the LAIR-1 ligation led to a strong inhibition of both GM-CSF receptor-mediated intracellular calcium increases, phosphorylation and activation of Akt1/protein kinase B alpha, a substrate of the phosphatidylinositol-3 kinase. This last inhibitory effect was prevented by a synthetic peptide spanning the ITIM portion of LAIR-1, suggesting the involvement of SHP-1 phosphatase in LAIR-1-mediated inhibitory signal. Altogether, these findings indicate that the engagement of LAIR-1 can down-regulate GM-CSF-mediated survival and proliferation of AML blasts, suggesting an additional therapeutic approach to the treatment of AML patients.
AB - The leukocyte-associated Ig-like receptor-1 (LAIR-1), a surface leukocyte receptor containing two immune receptor tyrosine-based inhibitory motif (ITIM) is expressed on acute myeloid leukemia (AML) blasts isolated from peripheral blood or bone marrow of 17 patients (2 MO, 3 M1, 5 M2, 2 M4 and 5 M5 acording to French, American and British classification). Further, we provide evidence that LAIR-1 engagement inhibits granulocyte-monocyte colony-stimulating factor (GM-CSF)-induced proliferation of AML blasts. Indeed, leukemia cells stimulated with GM-CSF were blocked in the G0/G1 phase of the cell cycle and underwent apoptosis within 4 days after the engagement of LAIR-1. Remarkably, LAIR-1 was functional also in AML blasts which do not express CD33, mainly M4 and M5. Importantly, the LAIR-1 ligation led to a strong inhibition of both GM-CSF receptor-mediated intracellular calcium increases, phosphorylation and activation of Akt1/protein kinase B alpha, a substrate of the phosphatidylinositol-3 kinase. This last inhibitory effect was prevented by a synthetic peptide spanning the ITIM portion of LAIR-1, suggesting the involvement of SHP-1 phosphatase in LAIR-1-mediated inhibitory signal. Altogether, these findings indicate that the engagement of LAIR-1 can down-regulate GM-CSF-mediated survival and proliferation of AML blasts, suggesting an additional therapeutic approach to the treatment of AML patients.
KW - Acute myleoid leukemia
KW - Apoptosis
KW - Cell proliferation
KW - GM-CSF receptor
KW - Poshpatidylinositol-3-kinase
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U2 - 10.1002/1521-4141(200112)31:12<3667::AID-IMMU3667>3.0.CO;2-G
DO - 10.1002/1521-4141(200112)31:12<3667::AID-IMMU3667>3.0.CO;2-G
M3 - Article
C2 - 11745387
AN - SCOPUS:0035666865
VL - 31
SP - 3667
EP - 3675
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 12
ER -