Faculty, Staff and Student Publications
Publication Date
12-20-2024
Journal
iScience
Abstract
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.
Keywords
Biological sciences, Computer science, Natural sciences
DOI
10.1016/j.isci.2024.111242
PMID
39628582
PMCID
PMC11613170
PubMedCentral® Posted Date
10-28-2024
PubMedCentral® Full Text Version
Post-print
Graphical Abstract
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Medical Sciences Commons, Oncology Commons
