The cell polarity PTK7 receptor acts as a modulator of the chemotherapeutic response in acute myeloid leukemia and impairs clinical outcome

Thomas Prebet, Anne Catherine Lhoumeau, Christine Arnoulet, Anaïs Aulas, Sylvie Marchetto, Stéphane Audebert, Francesca Puppo, Christian Chabannon, Danielle Sainty, Marie Josée Santoni, Michael Sebbagh, Virginia Summerour, Yannick Huon, Won Sik Shin, Seung Taek Lee, Benjamin Esterni, Norbert Vey, Jean Paul Borg

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

The pseudo tyrosine kinase receptor 7 (PTK7) is an orphan tyrosine kinase receptor assigned to the planar cell polarity pathway. It plays a major role during embryogenesis and epithelial tissue organization. Here we found that PTK7 is also expressed in normal myeloid progenitors and CD34+ CD38 - bone marrow cells in humans. We performed an immunophenotyping screen on more than 300 patients treated for hematologic malignancies. We demonstrated that PTK7 is expressed in acute myeloid leukemia (AML) and is mostly assigned to granulocytic lineage differentiation. Patients with PTK7-positive AML are more resistant to anthracycline-based frontline therapy with a significantly reduced leukemia-free survival in a multivariate analysis model. In vitro, expression of PTK7 in cultured leukemia cells promotes cell migration, cell survival, and resistance to anthracycline-induced apoptosis. The intracellular region of PTK7 is required for these effects. Furthermore, we efficiently sensitized primary AML blasts to anthracycline-mediated cell death using a recombinant soluble PTK7-Fc protein. We conclude that PTK7 is a planar cell polarity component expressed in the myeloid progenitor compartment that conveys promigratory and antiapoptotic signals into the cell and that represents an independent prognosis factor of survival in patients treated with induction chemotherapy.

Original languageEnglish
Pages (from-to)2315-2323
Number of pages9
JournalBlood
Volume116
Issue number13
DOIs
Publication statusPublished - 2010 Sep 30

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Prebet, T., Lhoumeau, A. C., Arnoulet, C., Aulas, A., Marchetto, S., Audebert, S., Puppo, F., Chabannon, C., Sainty, D., Santoni, M. J., Sebbagh, M., Summerour, V., Huon, Y., Shin, W. S., Lee, S. T., Esterni, B., Vey, N., & Borg, J. P. (2010). The cell polarity PTK7 receptor acts as a modulator of the chemotherapeutic response in acute myeloid leukemia and impairs clinical outcome. Blood, 116(13), 2315-2323. https://doi.org/10.1182/blood-2010-01-262352