CD36 defines primitive chronic myeloid leukemia cells less responsive to imatinib but vulnerable to antibody-based therapeutic targeting
(2018) In Haematologica 103(3). p.447-455- Abstract
Tyrosine kinase inhibitors (TKIs) are highly effective for the treatment of chronic myeloid leukemia (CML), but very few patients are cured. The major drawbacks regarding TKIs are their low efficacy in eradicating the leukemic stem cells responsible for disease maintenance and relapse upon drug cessation. Herein, we performed ribonucleic acid sequencing of flow-sorted primitive (CD34+CD38low) and progenitor (CD34+CD38+) chronic phase CML cells, and identified transcriptional upregulation of 32 cell surface molecules relative to corresponding normal bone marrow cells. Focusing on novel markers with increased expression on primitive CML cells, we confirmed upregulation of the scavenger receptor... (More)
Tyrosine kinase inhibitors (TKIs) are highly effective for the treatment of chronic myeloid leukemia (CML), but very few patients are cured. The major drawbacks regarding TKIs are their low efficacy in eradicating the leukemic stem cells responsible for disease maintenance and relapse upon drug cessation. Herein, we performed ribonucleic acid sequencing of flow-sorted primitive (CD34+CD38low) and progenitor (CD34+CD38+) chronic phase CML cells, and identified transcriptional upregulation of 32 cell surface molecules relative to corresponding normal bone marrow cells. Focusing on novel markers with increased expression on primitive CML cells, we confirmed upregulation of the scavenger receptor CD36 and the leptin receptor by flow cytometry. We also delineate a subpopulation of primitive CML cells expressing CD36 that is less sensitive to imatinib treatment. Using CD36 targeting antibodies, we show that the CD36 positive cells can be targeted and killed by antibody-dependent cellular cytotoxicity. In summary, CD36 defines a subpopulation of primitive CML cells with decreased imatinib sensitivity that can be effectively targeted and killed using an anti-CD36 antibody.
(Less)
- author
- organization
-
- Division of Clinical Genetics
- Translational Genomic and Functional Studies of Leukemia (research group)
- Targeted therapies in leukemia (research group)
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
- publishing date
- 2018-02-28
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Haematologica
- volume
- 103
- issue
- 3
- pages
- 447 - 455
- publisher
- Ferrata Storti Foundation
- external identifiers
-
- pmid:29284680
- scopus:85042748161
- ISSN
- 0390-6078
- DOI
- 10.3324/haematol.2017.169946
- language
- English
- LU publication?
- yes
- id
- 27ac258d-e0d8-456b-a381-f589e912f131
- date added to LUP
- 2018-04-12 13:23:26
- date last changed
- 2024-08-19 16:33:38
@article{27ac258d-e0d8-456b-a381-f589e912f131, abstract = {{<p>Tyrosine kinase inhibitors (TKIs) are highly effective for the treatment of chronic myeloid leukemia (CML), but very few patients are cured. The major drawbacks regarding TKIs are their low efficacy in eradicating the leukemic stem cells responsible for disease maintenance and relapse upon drug cessation. Herein, we performed ribonucleic acid sequencing of flow-sorted primitive (CD34<sup>+</sup>CD38<sup>low</sup>) and progenitor (CD34<sup>+</sup>CD38<sup>+</sup>) chronic phase CML cells, and identified transcriptional upregulation of 32 cell surface molecules relative to corresponding normal bone marrow cells. Focusing on novel markers with increased expression on primitive CML cells, we confirmed upregulation of the scavenger receptor CD36 and the leptin receptor by flow cytometry. We also delineate a subpopulation of primitive CML cells expressing CD36 that is less sensitive to imatinib treatment. Using CD36 targeting antibodies, we show that the CD36 positive cells can be targeted and killed by antibody-dependent cellular cytotoxicity. In summary, CD36 defines a subpopulation of primitive CML cells with decreased imatinib sensitivity that can be effectively targeted and killed using an anti-CD36 antibody.</p>}}, author = {{Landberg, Niklas and von Palffy, Sofia and Askmyr, Maria and Lilljebjörn, Henrik and Sandén, Carl and Rissler, Marianne and Mustjoki, Satu and Hjorth-Hansen, Henrik and Richter, Johan and Ågerstam, Helena and Järås, Marcus and Fioretos, Thoas}}, issn = {{0390-6078}}, language = {{eng}}, month = {{02}}, number = {{3}}, pages = {{447--455}}, publisher = {{Ferrata Storti Foundation}}, series = {{Haematologica}}, title = {{CD36 defines primitive chronic myeloid leukemia cells less responsive to imatinib but vulnerable to antibody-based therapeutic targeting}}, url = {{http://dx.doi.org/10.3324/haematol.2017.169946}}, doi = {{10.3324/haematol.2017.169946}}, volume = {{103}}, year = {{2018}}, }