WNT receptors profile expression in mature blood cells and immature leukemic cells: RYK emerges as a hallmark receptor of acute leukemia

Eur J Haematol. 2016 Aug;97(2):155-65. doi: 10.1111/ejh.12698. Epub 2015 Nov 30.

Abstract

Background: Wnt signaling induces a plethora of intracellular responses that dictate normal or abnormal cellular behavior. Abnormal WNT signaling has been related to the development of leukemogenic processes. In this regard, it is important to know the expression profile of WNT receptors in normal and malignant cells, in order to understand the WNT mechanisms that control the cell behavior. This work aimed to determine the WNT receptors expression profile in normal and leukemia cells.

Methods: Expression of WNT receptors was determined by flow cytometry using leukemia-derived cell lines, peripheral blood cells, and blood marrow samples from healthy volunteers and acute leukemia patients.

Results: Despite the heterogenic WNT receptors expression in mature normal blood cells and in immature tumorigenic cells, the RYK receptor was found highly express in leukemia cells, but not in normal cells. RYK expression was found mainly in cells positive to immature markers like CD33, CD13, CD7, and CD117.

Conclusions: Our data show differences in FZD receptors expression between T and B leukemic cells, but both cell types and also myeloblast-derived cells express high levels of RYK. The association of RYK expression with immature markers indicates its possible use as a diagnostic marker or therapeutic target.

Keywords: RYK; WNT; bone marrow; leukemia; lymphocytes; mature blood cells.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor
  • Blood Cells / metabolism*
  • Cell Differentiation / genetics
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Female
  • Gene Expression
  • Humans
  • Immunophenotyping
  • Leukemia / diagnosis
  • Leukemia / genetics*
  • Leukemia / metabolism
  • Male
  • Middle Aged
  • Phenotype
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptors, Wnt / genetics*
  • Receptors, Wnt / metabolism
  • Signal Transduction
  • Transcriptome*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Receptors, Wnt
  • RYK protein, human
  • Receptor Protein-Tyrosine Kinases