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Thoas Fioretos

Thoas Fioretos

Research team manager

Thoas Fioretos

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

Author

  • Niklas Landberg
  • Sofia von Palffy
  • Maria Askmyr
  • Henrik Lilljebjörn
  • Carl Sandén
  • Marianne Rissler
  • Satu Mustjoki
  • Henrik Hjorth-Hansen
  • Johan Richter
  • Helena Ågerstam
  • Marcus Järås
  • Thoas Fioretos
Show all

Summary, in English

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.

Department/s

  • Division of Clinical Genetics
  • Translational Genomic and Functional Studies of Leukemia
  • Targeted therapies in leukemia
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy

Publishing year

2018-02-28

Language

English

Pages

447-455

Publication/Series

Haematologica

Volume

103

Issue

3

Document type

Journal article

Publisher

Ferrata Storti Foundation

Topic

  • Hematology

Status

Published

Research group

  • Translational Genomic and Functional Studies of Leukemia
  • Targeted therapies in leukemia

ISBN/ISSN/Other

  • ISSN: 0390-6078