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

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http://hdl.handle.net/10138/234418

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Landberg , N , von Palffy , S , Askmyr , M , Lilljebjorn , H , Sanden , C , Rissler , M , Mustjoki , S , Hjorth-Hansen , H , Richter , J , Agerstam , H , Jaras , M & Fioretos , T 2018 , ' CD36 defines primitive chronic myeloid leukemia cells less responsive to imatinib but vulnerable to antibody-based therapeutic targeting ' , Haematologica , vol. 103 , no. 3 , pp. 447-455 . https://doi.org/10.3324/haematol.2017.169946

Title: CD36 defines primitive chronic myeloid leukemia cells less responsive to imatinib but vulnerable to antibody-based therapeutic targeting
Author: Landberg, Niklas; von Palffy, Sofia; Askmyr, Maria; Lilljebjorn, Henrik; Sanden, Carl; Rissler, Marianne; Mustjoki, Satu; Hjorth-Hansen, Henrik; Richter, Johan; Agerstam, Helena; Jaras, Marcus; Fioretos, Thoas
Contributor: University of Helsinki, Medicum
Date: 2018-02-28
Language: eng
Number of pages: 9
Belongs to series: Haematologica
ISSN: 0390-6078
URI: http://hdl.handle.net/10138/234418
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(+) CD38(low)) 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 anti-bodies, 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 anti-body.
Subject: STEM-CELLS
LEPTIN RECEPTOR
BCR-ABL
CML
IDENTIFICATION
PERSISTENCE
EXPRESSION
DISEASE
MICE
3122 Cancers
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