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Schulz, M. ; Bleser, S. ; Groels, M. ; Bošnački, D.* ; Burger, J.A.* ; Chiorazzi, N.* ; Marr, C.

Mathematical multi-compartment modeling of chronic lymphocytic leukemia cell kinetics under ibrutinib.

iScience 27:111242 (2024)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The Bruton tyrosine kinase inhibitor ibrutinib is an effective treatment for patients with chronic lymphocytic leukemia (CLL). While it rapidly reduces lymph node and spleen size, it initially increases the number of lymphocytes in the blood due to cell redistribution. A previously published mathematical model described and quantified those cell kinetics. Here, we propose an alternative mechanistic model that outperforms the previous model in 26 of 29 patients. Our model introduces constant subcompartments for healthy lymphocytes and benign tissue and treats spleen and lymph nodes as separate compartments. This three-compartment model (comprising blood, spleen, and lymph nodes) performed significantly better in patients without a mutation in the IGHV gene, indicating a diverse response to ibrutinib for cells residing in lymph nodes and spleen. Additionally, high ZAP-70 expression was linked to less cell death in the spleen. Overall, our study enhances understanding of CLL genetics and patient response to ibrutinib and provides a framework applicable to the study of similar drugs.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Biological Sciences ; Computer Science ; Natural Sciences; Therapy; Blood
ISSN (print) / ISBN 2589-0042
e-ISSN 2589-0042
Zeitschrift iScience
Quellenangaben Band: 27, Heft: 12, Seiten: , Artikelnummer: 111242 Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam ; Bosten ; London ; New York ; Oxford ; Paris ; Philadelphia ; San Diego ; St. Louis
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of AI for Health (AIH)
Förderungen Hightech Agenda Bayern
European Research Council (ERC)