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CD36 defines primitive chronic myeloid leukemia cells less responsive to imatinib but vulnerable to antibody-based therapeutic targeting

Landberg, Niklas LU ; von Palffy, Sofia LU ; Askmyr, Maria LU ; Lilljebjörn, Henrik LU ; Sandén, Carl LU ; Rissler, Marianne LU ; Mustjoki, Satu; Hjorth-Hansen, Henrik; Richter, Johan LU and Ågerstam, Helena LU , et al. (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.

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Contribution to journal
publication status
published
subject
in
Haematologica
volume
103
issue
3
pages
447 - 455
publisher
Ferrata Storti Foundation
external identifiers
  • scopus:85042748161
ISSN
0390-6078
DOI
10.3324/haematol.2017.169946
language
English
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yes
id
27ac258d-e0d8-456b-a381-f589e912f131
date added to LUP
2018-04-12 13:23:26
date last changed
2019-01-06 13:50:59
@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},
  volume       = {103},
  year         = {2018},
}