SWATH-proteomics analysis of ibrutinib mechanism of action in neutropenia and acute myeloid leukemia initiating mutated granulocyte-colony stimulating factor receptor

Neutrophil production and function are primarily determined by granulocyte colony stimulating factor receptor (G-CSFR). G-CSFRs associated mutations (mostly localized in the transmembrane and cytoplasmic domains of the receptor) have been reported with several distinct hematological abnormalities as well as malignancies, e.g. severe congenital neutropenia (SCN), acute myeloid leukemia (AML) and chronic neutrophilic leukemia (CNL). Ibrutinib, a small molecule Bruton’s tyrosine kinase (BTK) inhibitor, is FDA approved and clinically used against B-cell related leukemia. In our previous published work (Dwivedi et al., Leukemia.2019;33:75–87), we have shown ibrutinib’s efficacy in the mutated G-CSFRs based leukemia model systems (mouse and human). However, the signaling mechanism of ibrutinib’s efficacy is not explored yet. Here, we present a unique SWATH-based label free quantitative proteomics analysis of the normal and mutated G-CSFRs signaling post ibrutinib treatment, using 32D cell-line-based in vitro model system.