Targeting chronic lymphocytic leukemia with N-methylated thrombospondin-1–derived peptides overcomes drug resistance

Author:

Pramil Elodie12,Herbi Bastian Linda1,Denèfle Thomas2ORCID,Nemati Fariba3,Xiao Malina1,Lardé Eva2,Maloum Karim4ORCID,Roos-Weil Damien15ORCID,Chapiro Elise14ORCID,Le Garff-Tavernier Magali14ORCID,Davi Frédéric14,Decaudin Didier36,Sarfati Marika7ORCID,Nguyen-Khac Florence14ORCID,Merle-Béral Hélène14ORCID,Karoyan Philippe289ORCID,Susin Santos A.1ORCID

Affiliation:

1. Centre de Recherche des Cordeliers, Cell Death and Drug Resistance in Hematological Disorders Team, INSERM UMRS_1138, Sorbonne Université, Université Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot, Paris, France;

2. Sorbonne Université, Ecole Normale Supérieure, Paris Sciences & Lettres University Paris, Centre National de la Recherche Scientifique, Laboratoire des Biomolécules, Paris, France;

3. Laboratory of Preclinical Investigation, Department of Translational Research, Institut Curie, Paris Sciences & Lettres University Paris, Paris, France;

4. Assistance Publique–Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Service d’Hématologie Biologique, Paris, France;

5. Assistance Publique–Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Service d’Hématologie Clinique, Paris, France;

6. Department of Medical Oncology, Institut Curie, Paris, France;

7. Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, Canada;

8. Kayvisa, AG, Zug, Switzerland; and

9. Kaybiotix, GmbH, Baar, Switzerland

Abstract

Key PointsN-methylated thrombospondin-1 mimetic peptides selectively kill the leukemic CD5+ B cells, sparing mature and precursor nontumor cells. CD47 peptide triggering eliminates drug-resistant CLL cells by inducing an original form of cell death regulated by G proteins.

Publisher

American Society of Hematology

Subject

Hematology

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