The cell polarity PTK7 receptor acts as a modulator of the chemotherapeutic response in acute myeloid leukemia and impairs clinical outcome
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.
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PTK7 is upregulated in many common cancers including T-ALL and is a potential biomarker of T-ALL.
“PTK7 is a transmembrane receptor that is upregulated in many common cancers including acute T-lymphocytic leukemia (T-ALL) and is a potential biomarker of T-ALL.259”
From Smart nanoparticles for cancer therapy (2023) · cites this paper as [259]
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“Similarly, high protein tyrosine kinase 7 (PTK7) expression has been associated with improved disease-free survival in breast cancer patients receiving taxanebased chemotherapy, but with worse disease-free survival in breast cancer or acute myeloid leukemia patients receiving anthracycline chemotherapy [34, 35].”
Background
- Authors
- 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.
- Affiliations
- Inserm U891, Centre de Recherche en Cancérologie de Marseille, Marseille, France;
- Inserm (FR)
- Institut Paoli-Calmettes (FR)
- Yonsei University (KR)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2010-09-30
- Volume
- 116
- Issue
- 13
- Pages
- 2315-2323
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2002387564
- Cited by
- 102
- References
- 42
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 7 · 2019: 11 · 2018: 6 · 2017: 5 · 2016: 6 · 2015: 10 · 2014: 8 · 2013: 5 · 2012: 12
- FWCI
- 4.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Health Sciences › Medicine › Hematology › Chronic Myeloid Leukemia Treatments
- Keywords
- PTK7, acute myeloid leukemia, planar cell polarity, receptor tyrosine kinase, anthracycline resistance, chemotherapy response, leukemia-free survival, prognostic factors, cell migration, apoptosis resistance, myeloid progenitor cells, granulocytic differentiation
- MeSH terms
- Antibiotics, Antineoplastic, Base Sequence, Cell Movement, Humans, Prognosis, Leukemia, Myeloid, Acute, Cell Adhesion Molecules, Immunophenotyping, Cell Polarity, Treatment Outcome, Apoptosis, DNA Primers, HL-60 Cells, Anthracyclines, Drug Resistance, Neoplasm, Jurkat Cells, K562 Cells, U937 Cells, Cytogenetic Analysis, Receptor Protein-Tyrosine Kinases, Cell Line, Tumor, In Vitro Techniques
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