Publication: SWATH-Proteomics of Ibrutinib's Action in Myeloid Leukemia Initiating Mutated G-CSFR Signaling
Issued Date
2020-01-01
Resource Type
ISSN
18628354
18628346
18628346
Other identifier(s)
2-s2.0-85085485085
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Proteomics - Clinical Applications. (2020)
Suggested Citation
Pankaj Dwivedi, Somchai Chutipongtanate, David E. Muench, Mohammad Azam, Harry Leighton Grimes, Kenneth D. Greis SWATH-Proteomics of Ibrutinib's Action in Myeloid Leukemia Initiating Mutated G-CSFR Signaling. Proteomics - Clinical Applications. (2020). doi:10.1002/prca.201900144 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/57758
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
SWATH-Proteomics of Ibrutinib's Action in Myeloid Leukemia Initiating Mutated G-CSFR Signaling
Abstract
© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Purpose: To evaluate cellular protein changes in response to treatment with an approved drug, ibrutinib, in cells expressing normal or mutated granulocyte-colony stimulating factor receptor (G-CSFR). G-CSFR mutations are associated with some hematological malignancies. Previous studies show the efficacy of ibrutinib (a Bruton's tyrosine kinase inhibitor) in mutated G-CSFR leukemia models but do not address broader signaling mechanisms. Experimental Design: A label-free quantitative proteomics workflow to evaluate the cellular effects of ibrutinib treatment is established. This includes three biological replicates of normal and mutated G-CSFR expressed in a mouse progenitor cell (32D cell line) with and without ibrutinib treatment. Results: The proteomics dataset shows about 1000 unique proteins quantified with nearly 400 significant changes (p value < 0.05), suggesting a highly dynamic network of cellular signaling in response to ibrutinib. Importantly, the dataset is very robust with coefficients of variation for quantitation at 13.0–20.4% resulting in dramatic patterns of protein differences among the groups. Conclusions and Clinical Relevance: This robust dataset is available for further mining, hypothesis generation, and testing. A detailed understanding of the restructuring of the proteomics signaling cascades by ibrutinib in leukemia biology will provide new avenues to explore its use for other related malignancies.