Ex vivo drug response profiling detects recurrent sensitivity patterns in drug-resistant acute lymphoblastic leukemia

Author:

Frismantas Viktoras12,Dobay Maria Pamela3,Rinaldi Anna12,Tchinda Joelle12,Dunn Samuel H.4,Kunz Joachim5,Richter-Pechanska Paulina5,Marovca Blerim12,Pail Orrin12,Jenni Silvia12,Diaz-Flores Ernesto6,Chang Bill H.7,Brown Timothy J.8ORCID,Collins Robert H.8,Uhrig Sebastian9,Balasubramanian Gnana P.9,Bandapalli Obul R.5,Higi Salome12,Eugster Sabrina12,Voegeli Pamela10,Delorenzi Mauro311,Cario Gunnar12,Loh Mignon L.13,Schrappe Martin12,Stanulla Martin14,Kulozik Andreas E.5,Muckenthaler Martina U.5,Saha Vaskar1516,Irving Julie A.17,Meisel Roland18,Radimerski Thomas19,Von Stackelberg Arend92021,Eckert Cornelia92021,Tyner Jeffrey W.22,Horvath Peter2324,Bornhauser Beat C.12,Bourquin Jean-Pierre12ORCID

Affiliation:

1. Department of Oncology, and

2. Children’s Research Center, University Children’s Hospital Zurich, Zurich, Switzerland;

3. Swiss Institute of Bioinformatics, Lausanne, Switzerland;

4. School of Medicine, The University of Texas Southwestern Medical Center, Dallas, TX;

5. Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany;

6. Department of Pediatrics and Helen Diller Family Comprehensive Cancer Center, University of California–San Francisco, San Francisco, CA;

7. Division of Hematology and Oncology, Department of Pediatrics, Doernbecher Children’s Hospital, Oregon Health & Science University, Portland, OR;

8. Division of Hematology and Oncology, Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, TX;

9. German Cancer Research Center, Heidelberg, Germany;

10. Institute of Forensic Medicine, University of Zurich, Zurich, Switzerland;

11. Ludwig Center for Cancer Research, University of Lausanne, Lausanne, Switzerland;

12. Department of Pediatrics, University Medical Centre Schleswig-Holstein, Kiel, Germany;

13. Department of Pediatrics, University of California–San Francisco, San Francisco, CA;

14. Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany;

15. Division of Molecular and Clinical Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom;

16. Tata Translational Cancer Research Centre, Tata Medical Centre, Kolkata, India;

17. Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom;

18. Division of Pediatric Stem Cell Therapy, Clinic for Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany;

19. Disease Area Oncology, Novartis Institutes for Biomedical Research, Basel, Switzerland;

20. Department of Pediatric Oncology/Hematology, Charité Universitätsmedizin Berlin, Berlin, Germany;

21. German Cancer Consortium, Heidelberg, Germany;

22. Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR;

23. Synthetic and Systems Biology Unit, Hungarian Academy of Sciences, Biological Research Center, Szeged, Hungary; and

24. Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland

Abstract

Key Points Ex vivo drug profiling captures disease-relevant features and relevant sensitivity to therapeutic agents in ALL. A subset of drug-resistant T-ALL without mutations in ABL1 is highly responsive to dasatinib, which provides a rationale for drug repurposing.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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