Phosphatidylserine and Tyro3-Axl-Mertk Receptor Tyrosine Kinase level detection in plasma and on plasma-derived extracellular vesicle surface in chronic lymphocytic leukemia

Cell Biochem Funct. 2024 Jun;42(4):e4035. doi: 10.1002/cbf.4035.

Abstract

Chronic lymphocytic leukemia (CLL) is a chronic lymphoproliferative disorder characterized by monoclonal B cell proliferation. Studies carried out in recent years suggest that extracellular vesicles (EVs) may be a potential biomarker in cancer. Tyro3-Axl-Mertk (TAM) Receptor Tyrosine Kinases (RTKs) and Phosphatidylserine (PS) have crucial roles in macrophage-mediated immune response under normal conditions. In the tumor microenvironment, these molecules contribute to immunosuppressive signals and prevent the formation of local and systemic antitumor immune responses. Based on this, we aimed to evaluate the amount of PS and TAM RTK in plasma and on the surface of EVs in CLL patients and healthy volunteers in this study. In this study, 25 CLL (11 F/14 M) patients in the Rai (O-I) stage, newly diagnosed or followed up without treatment, and 15 healthy volunteers (11 F/4 M) as a control group were included. For all samples, PS and TAM RTK levels were examined first in the plasma and then in the EVs obtained from the plasma. We detected a significant decrease in plasma PS, and TAM RTK levels in CLL patients compared to the control. Besides, we determined a significant increase in TAM RTK levels on the EV surface in CLL, except for PS. In conclusion, these receptor levels measured by ELISA in plasma may not be effective for the preliminary detection of CLL. However, especially TAM RTKs on the surface of EVs may be good biomarkers and potential targets for CLL therapies.

Keywords: Phosphatidylserine (PS); Receptor Tyrosine Kinase (RTK); Tyro3‐Axl‐MerTK (TAM); chronic lymphocytic leukemia (CLL); extracellular vesicles (EVs).

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Axl Receptor Tyrosine Kinase
  • Extracellular Vesicles* / chemistry
  • Extracellular Vesicles* / metabolism
  • Female
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell* / blood
  • Leukemia, Lymphocytic, Chronic, B-Cell* / diagnosis
  • Leukemia, Lymphocytic, Chronic, B-Cell* / metabolism
  • Male
  • Middle Aged
  • Phosphatidylserines* / blood
  • Phosphatidylserines* / metabolism
  • Proto-Oncogene Proteins / blood
  • Proto-Oncogene Proteins / metabolism
  • Receptor Protein-Tyrosine Kinases* / blood
  • Receptor Protein-Tyrosine Kinases* / metabolism
  • c-Mer Tyrosine Kinase / metabolism

Substances

  • Phosphatidylserines
  • Receptor Protein-Tyrosine Kinases
  • Axl Receptor Tyrosine Kinase
  • AXL protein, human
  • TYRO3 protein, human
  • Proto-Oncogene Proteins
  • c-Mer Tyrosine Kinase
  • MERTK protein, human