[leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1) inhibits proliferation and promotes apoptosis of human HEL cells with JAK2 V617F mutation by blocking the JAK/STAT and PI3K/AKT signaling pathways]

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2024 Mar;40(3):207-214.
[Article in Chinese]


Objective To investigate the role of human leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) in the regulation of Janus kinase/signal transducers and activators of transcription (JAK/STAT) and phosphatidylinositol 3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT /mTOR) signaling pathways in human acute myeloid leukemia HEL cells carrying the JAK2 V617F mutation, along with its effects on cell proliferation and apoptosis. MethodsThe JAK2 V617F mutation was identified using reverse transcription PCR and gene sequencing. The protein phosphatase (PTP) recruited by LAIR-1 was determined through co-immunoprecipitation and Western blot analysis. The proliferation of HEL cells was detected by CCK-8 assay. The apoptosis rate of HEL cells was detected by flow cytometry with annexin V-FITC/PI labeling. Western blot analysis was employed to assess the phosphorylation status of proteins involved in the JAK/STAT and PI3K/AKT/mTOR pathways, as well as the expression levels of cyclinD1, B cell lymphoma 2 (Bcl2), and Bcl2 associated X protein (BAX). Results In HEL cells containing the JAK2 V617F mutation, LAIR-1 was observed to recruit SH2-containing protein tyrosine phosphatase 2 (SHP-2) upon binding with its ligand collagen. Moreover, LAIR-1 downregulated the tyrosine phosphorylation levels of JAK2, STAT1, STAT3, STAT5, AKT and mTOR and significantly reduced the expression of cyclin D1 and Bcl2, while having no effect on the expression of BAX. In addition, LAIR-1 exhibited a significantly inhibitory effect on cell proliferation and promoted apoptosis in HEL cells. Conclusion In HEL cells with JAK2 V617F mutation, LAIR-1 can inhibit the activation of JAK/STAT and PI3K/AKT/mTOR signaling pathways by recruiting SHP-2, thereby inhibiting the proliferation of HEL cells and promoting cell apoptosis.

Publication types

  • English Abstract

MeSH terms

  • Apoptosis
  • Humans
  • Janus Kinase 2 / genetics
  • Mutation
  • Phosphatidylinositol 3-Kinases*
  • Proto-Oncogene Proteins c-akt*
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Immunologic*
  • Signal Transduction
  • TOR Serine-Threonine Kinases
  • bcl-2-Associated X Protein


  • bcl-2-Associated X Protein
  • leukocyte-associated immunoglobulin-like receptor 1
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-bcl-2
  • JAK2 protein, human
  • Janus Kinase 2
  • Receptors, Immunologic