Chemo-Click: Receptor-Controlled\nand Bioorthogonal\nChemokine Ligation for Real-Time Imaging of Drug-Resistant Leukemic\nB Cells

Drug resistance in\nB cell leukemia is characterized by\nthe coexpression\nof CXCR5 and CXCR3 chemokine receptors, making it a valuable biomarker\nfor patient stratification. Herein, we report a novel platform of\nactivatable chemokines to selectively image drug-resistant leukemic\nB cells for the first time. The C-terminal derivatization of the human\nchemokines CXCL13 and CXCL10 with bioorthogonal tetrazine-BODIPY and\nBCN groups retained binding and internalization via their cognate\nCXCR5 and CXCR3 receptors and enabled rapid fluorescence labeling\nof CXCR5+ CXCR3+ resistant B cellsbut not drug-susceptible\nleukemic cellsvia intracellular chemokine ligation. This modular\nchemical approach offers a versatile strategy for real-time immunophenotyping\nof cell populations with distinct chemokine profiles and will accelerate\nthe design of new precision medicine tools to advance personalized\ntherapies in blood tumors.