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

M. Raffaella Zocchi, Fabio Pellegatta, Ivana Pierri, Marco Gobbi, Alessandro Poggi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)3667-3675
Number of pages9
JournalEuropean Journal of Immunology
Volume31
Issue number12
DOIs
Publication statusPublished - 2001

Keywords

  • Acute myleoid leukemia
  • Apoptosis
  • Cell proliferation
  • GM-CSF receptor
  • Poshpatidylinositol-3-kinase

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this