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

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 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.

journal_name

Haematologica

journal_title

Haematologica

authors

Landberg N,von Palffy S,Askmyr M,Lilljebjörn H,Sandén C,Rissler M,Mustjoki S,Hjorth-Hansen H,Richter J,Ågerstam H,Järås M,Fioretos T

doi

10.3324/haematol.2017.169946

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

447-455

issue

3

eissn

0390-6078

issn

1592-8721

pii

haematol.2017.169946

journal_volume

103

pub_type

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